| Abstract|| |
Background: Meningococcal meningitis (MM) persists in developing countries in forms of outbreaks, epidemics or sporadic cases, resulting in considerable morbidity and mortality. The aim of this study is to evaluate the clinical and laboratory aspects of adults and children with MM. Materials and Methods: This is a retrospective study with 291 patients diagnosed with MM, hospitalized in a tertiary hospital in Fortaleza, Northeast of Brazil, between 1999 and 2009. We analyzed epidemiological, clinical and laboratory findings. Results: The mean age of patients was 13.7 ± 12.8 years, ranging from newborn to 71 years, 59% were 12 or less, mostly male (57.3%). Average time between symptom onset and hospitalization was 2.21 ± 2.62 days. There was associated meningococcemia at 22.3% of cases. The most common manifestations were fever (92.7%), vomiting (80.4%), headache (68.7%), neck stiffness (64.9%) and petechiae (31.9%). Laboratory tests showed an average Hb 11.1 ± 1.7 g/dL, WBC 17.94 ± 17.29 x 10/mm, platelets 20.58 ± 11.53 x 103/mm3. Sodium (134.66 ± 14.89 mEq/l), potassium (4.2315 ± 3.8805 mEq/l), urea (35.66 ± 35.96 mg/dl), creatinine (0.77 ± 0.77 mg/dl), AST (48.81 ± 62.73 units/L), and ALT (37.93 ± 36.78 units/L) were other laboratory parameters. There was record of 25 deaths (8.5%). Conclusion: Most were children below 12 years, suggesting the vulnerability of this age group for MM. There was no statistical difference between adults and children with regard to laboratorial parameters, but the data show numbers that can represent a laboratory profile of the disease.
Keywords: Clinical Manifestations, epidemiology, laboratory changes, meningitis, meningococcemia
|How to cite this article:|
Daher EF, Maia RC, Ciarlini BS, da Silva SL, da Silva EC, Silva Junior GB. Clinical and laboratory aspects of adults and children admitted with meningococcal meningitis to a tertiary hospital in Fortaleza, Ceara, Brazil. Ann Trop Med Public Health 2012;5:483-8
|How to cite this URL:|
Daher EF, Maia RC, Ciarlini BS, da Silva SL, da Silva EC, Silva Junior GB. Clinical and laboratory aspects of adults and children admitted with meningococcal meningitis to a tertiary hospital in Fortaleza, Ceara, Brazil. Ann Trop Med Public Health [serial online] 2012 [cited 2018 Nov 17];5:483-8. Available from: http://www.atmph.org/text.asp?2012/5/5/483/105139
| Introduction|| |
The gram-negative bacteria Neisseria More Details meningitidis (meningococcus) is part of the normal bacterial flora of the upper respiratory tract. It is Meningococcal Disease (MD) any infections caused by meningococcus, including conjutive, septic arthritis, meningitis and septicemia (meningococcemia).  The invasive infection results in severe clinical spectrum, including meningitis and septicemia, which meningitis is the clinical form most frequent. 
Meningitis can be caused by many infectious agents like bacteria, viruses and fungi, and non-infectious factors (like trauma). Meningococcal Meningitis is one of the most common: for example, accounts for up to 95% in epidemics of meningitis in the "African Meningitis Belt". 
Fever, headache and stiff neck often suggests the diagnosis of meningitis. The clinical manifestations may vary according to age range. In infants, fever and vomiting are frequently the early complaints, while in the elderly are more often - in addition to fever - mental confusion, numbness and disorientation. With a better understanding of the pathophysiology of the disease, the efficacy of treatment has advanced. The early and adequate antibiotic therapy is undoubtedly an essential factor for therapeutic success. 
This paper presents clinical and laboratory findings in 291 patients with meningococcal meningitis in a metropolitan city of northeastern Brazil. The aim of this study is to evaluate the clinical and laboratory aspects of adults and children with MM [Table 1].
|Table 1: Clinical findings presented by patients with meningococcal meningitis in Fortaleza, Brazil|
Click here to view
| Materials and Methods|| |
A retrospective study with 291 patients diagnosed with meningococcal meningitis at the Hospital Sao Jose of Infectious Diseases, in the city of Fortaleza, northeast Brazil, from January 1999 to December 2009. Patients with clinical-epidemiological diagnosis, and laboratories and clinics data registered in medical records were included, and excluded those who had not. This research was reviewed and approved by the ethics committee on research involving human institution.
Variables such as age, sex, origin, profession, time between symptom onset and hospitalization, length of hospitalization, vital signs (maximum and minimum values during hospitalization), clinical manifestations, antibiotic adopted and laboratory data were analyzed. This laboratory data are: blood counts, serum electrolytes (sodium, potassium), urea and serum creatinine, AST, ALP and urinalysis. The cerebrospinal fluid (CSF) data was also analyzed, regarding the cellular, biochemical, and isolation of bacterial meningitis meningococcus. For statistical analysis, patients were divided into younger than 12 years and older than 12 years.
Data were classified using the programs Excel version 2003 and Epi Info 6.04b, 2001 (Centers for Disease Control and Prevention, USA). Statistical analysis was configured by using the chi-square or Fisher exact test for qualitative variables asssoation. Results were considered significant at p <0.05.
| Results|| |
The study included 291 patients, mean age 13.7 ± 12.8 years, ranging from less than one year old (17 patients) to 71 years; 213 patients were under 18 years (73% of the sample). There was a slight preponderance of coming from the state capital, Fortaleza (55.7% versus 44.3% of the interior of the state). Most patients were male (57.6%).
Among the 291 patients studied, 65 (22.3%) had associated meningococcemia. The average number of days between the onset of symptoms and hospitalization was 2.2 ± 2.6 days (ranging from less than 12 hours to 30 days). The average length of stay was 10.73 ± 7.13 days. This average was 11.53 ± 8.11 in patients who had sepsis associated, against 10.54 ± 6.86 in those who had only meningitis (p = 0.0002).
The most common clinical manifestations at admission were fever (92.78%), vomiting (80.41%), headache (68.73%), neck stiffness (64.95%), petechiae (64.95%), and the presence of Brudzinski sign (30.58%), ecchymosis (27.15%) and somnolence (26.46%).
According to the hospital's medical records, lumbar puncture was performed in 263 patients - 90.4% of the total, 107 of which were older than 12 years (89.9% of this age group), and 156 younger than 12 years (90.7%). In the analysis of cerebrospinal fluid (CSF), the average cellularity found was 9923 ± 14212 cells. The average percentage in cells analysis was: 12.1 ± 19.5% lymphocytes, 3.0 ± 7.0% monocytes, and 83.6 ± 22.8% neutrophils. About biochemistry, the average glucose value was 30.9 ± 32.9, and protein, 224.4 ± 208.6.
Also in relation to CSF analysis, there are records of the study of the infectious agent at the beginning of treatment in 203 patients: N. Meningitidis was identified in 72 of these (35.4%). The gram stain identified gram-negative diplococci in 168 of 203 patients (84%). A second lumbar puncture was performed in 11 patients after the initiation of treatment, when the agent was again isolated in five patients, and gram stain showed diplococci in eight. There was no statistical difference between older and younger than 12 years of age in relation to the findings of the CSF.
About complete blood count (CBC), mean hemoglobin was 11.1 ± 1.7 g/dL. There were records of white blood cell count on admission of 276 patients (94.8%), with leukocytes above 10.000/mm³ in 202 (73.1%); 36 of the 268 patients who had record of platelet counts were less than 100,000/mm 3 (13.43%).
Acute kidney injury (AKI) was found in 10 cases (3.4%) at hospital admission, and they were in "Injury" (50%) and "Failure" (50%). Complete recovery of renal function at the moment of hospital discharge was observed in only 2 cases (20%). The average values of other laboratory parameters are showed in [Table 2].
|Table 2: Laboratory findings during hospital stay in patients with meningococcal meningitis in Fortaleza, Brazil|
Click here to view
The most used antibiotics were ceftriaxone (133 patients) and Crystalline Penicillin (164 pacients). Cefepime (25 patients), meropenem (3), ketoconazole (2), and ampicillin, ciprofloxacin, chloramphenicol and clindamycin (one each) were also used by the patients in the sample. Dexamethasone was used in 163 patients. There was record of 25 deaths in the period analyzed in this study (8.5%).
| Discussion|| |
This study evaluated a group of patients with meningococcal disease in a metropolitan area of northeastern Brazil. A research about the incidence and deaths from Meningococcal Disease (MD) in another region of Brazil (Sao Paulo) during the twentieth century showed a constant presence of disease (with four epidemics associated with moments of civil unrest) and the invariant profile of affected with respect to age in endemic periods: there is a greater risk in infants under one year, with a reduction of risk with increasing age.  Low age, poverty, and males remain as risk factors associated with MD and meningococcal meningitis (MM) in several studies. ,,,,
Although after the advent of antibiotics, there was a large decrease in fatality rate, and effective vaccine exists to prevent them,  MD, in the form of meningococcal meningitis, can still be regarded as a very serious illness. Different types of vaccines are available, and the success of these interventions has been proven, , including in the control of a community outbreak,  which reflects the decreasing incidence of the disease. Despite this, there are reports of outbreaks and epidemics, such as occurred in the state of Rio de Janeiro in the 1990 decade. 
The clinical diagnosis of MM can be done based on the presence of fever, rash, meningeal signs, leukocytosis, and altered mental status - independently the isolation of the infectious agent (on the CSF, on the blood etc).  In our study, the CSF culture was positive in 35.4% of patients who underwent lumbar puncture (72/203 of a total of 291).
In a series of 694 confirmed cases of meningitis (of various etiologies) in a Brazilian university hospital, meningococcal disease was diagnosed in 8.7%, with a mortality rate equal to 13.3%. Fever, vomiting and neck stiffness were associated with a lower chance of death in this series.  In another study, about 415 children with bacterial meningitis, the causal agent was definitively identified in 69.3%: meningococcus was found in 20.6%, with a mortality of 4.6%.This same study linked a decrease in positive blood cultures, both blood and CSF, with the use of empirical antimicrobial - 50.8 to 38.7% and 71.7 to 57.6%, respectively.  Donalisio et al.  had positive culture in 68.7% of 568 reported cases of meningococcal disease, and suggest that age and sex did not affect the chance to confirm the diagnosis of DM by culture of CSF or blood.
The culture was also positive in 77% of 233 cases of DM with meningitis and / or septicemia in a series from Malta,  while in another series, with children younger than 5 years in Oman, the agent was not identified in 52% cases of bacterial meningitis - MM represented 11% of this series. 
The mean length of hospitalization in our study was 10.73 ± 7.13 days. Prieto et al, found a mean of 12 days in patients with DM, the same number was pointed by Romanelli et al, in a series on evolution of bacterial meningitis in general. This last study, considering the etiology and the mean length of hospitalization of patients without complications (therefore excluding patients with complications and death) encountered 13.2 days, 8.4 days and 10.6 days for H. influenzae, N. meningitidis and S. pneumoniae, respectively.  Another study found that, unlike other age groups, in which most had length of stay less than or equal to 10 days (ranging from 87% in 10-14 years and 57% in those over 50), most patients with DM under one year old were hospitalized for more than 15 days - 41% in this age range, compared to 9% of the total, have a longer hospital stay. 
The average age in our sample was around 13 years, which in several series (with no age limits) was between 4-6. ,,,,, Nevertheless, authors point meningococco as the major cause of meningococcal meningitis in adults. ,
Mortality is associated with concomitance of meningococcemia serogroup B Neisseria meningitidis More Details, less than a year old and more than 30 years old. Other factors may be associated with more severe cases of the disease: for example, a study related to poor perfusion of cerebral capillaries due to the accession of N. meningitides,  and other related cortisol levels in the CSF (which in turn is related to the serum level) with the severity of bacterial meningitis. 
Stella-Silva et al,  made a comparison between the different clinical presentations of DM in a sample of 185 patients - 18% (DM with) meningitis, 62% meningitis and septicemia, 20% only (DM with) septicemia. In this series, the highest average number of leukocytes (blood cell count) was in patients who had both clinical forms (15348 leukocytes), and the highest average in relation to the average CSF cellularity was found in Meningitis (8350/mm 3 ). There was no difference regarding age or gender. These numbers are similar to those presented here, where the average value of leukocytes was 17948.75 ± 17298.36/mm 3 , and the average cellularity in the CSF analysis was 9923.20 ± 14212.58/mm 3 .
Also with regard to laboratory tests, study in Portugal found an average of 22,042/mm 3 white blood cell in 110 pediatric patients with bacterial meningitis (67% meningococcal meningitis, a percentage that differs from the Brazilian studies cited here) and an average of 2104 leukocytes/mm³ in CSF. The study also compared these values in patients with viral meningitis, finding an average of 13,233 blood leukocyte and 277 leukocytes / mm³ in CSF.  Also in relation to the CRL, the average glucose was 27.4 ± 11.7 to 318.0 ± 149.0 proteins and cells (per mm³) 5413.7 ± 3973.5 in a series on acute bacterial meningitis in infants. 
A study from Angola on bacterial meningitis in children (10%MM), found an average of 15,000 leukocytes in the blood and an average hemoglobin of 6.8g/dl in the CBC.  Heckenberger et al,  analyzing 253 cases of meningococcal meningitis in adults (mean age 36 ± 19 yrs) found a mean serum creatinine of 95mmol/l and sodium of 137mmol/L. Most patients who underwent lumbar puncture (80%, 195 of 242) had counts more than 999 cells in the CSF, with mean of 4.5g protein/l in this series. 
The frequency of signs and symptoms evident in our series is consistent with the expected in the medical literature. Fever, vomiting, headache, stiff neck are the four most common clinical manifestations of MM,  as well as in various bacterial meningitis in general. , Lucena et al,  also found, besides these four, seizures lowered level of consciousness and respiratory infection as the most frequent findings in a study involving infants with acute bacterial meningitis.
There are not many reports of AKI associated with MM: we found in our study 10 patients (3.4%) with acute kidney injury. In a study conducted in the same city as ours, Fortaleza, Brazil, 147 of 722 patients (17.7%), admitted to the infectious disease ICU, developed AKI. Meningitis was responsible for 8.2% of the causes of admission to the ICU and the main cause of AKI was sepsis in this series (41.5%). 
The use of dexamethasone is recommended in anti-inflammatory character in the management of bacterial meningitis, especially disease by Haemophilus influenzae children. This pratice is associated with the decrease the incidence of complications after the disease,  but the literature does not confirm decrease the frequency neurological sequelae, such as hearing loss, in meningococcal meningitis. 
In relation to antibiotic therapy, the current conduct relates to the use of antibiotics with good penetration in cerebrospinal fluid, such as ceftriaxone. In French series with 1344 patients with meningococcal meningitis (73% with positive culture), all strains were susceptible to cefotaxime and ceftriaxone, while 41.6% showed reduced susceptibility to penicillin, and 25.7% for amoxicillin.  Susceptibility profile similar was described in another French study. 
On the results presented here is worth noting that, despite penicillin was the antibiotic most common in the whole period (more than ceftriaxone in general), the use of the third-generation cephalosporin mentioned increased steadily over the years, being predominantly in the last years of our sample.
In summary, meningococcal meningitis remains an important public health problem in our environment, with significant morbidity and mortality. There were no significant differences of clinical and laboratory parameters analyzed between children and adults.
| References|| |
|1.||Hart CA. Infectious diseases: Meningococcal disease. West J Med 2000;173:125-8. |
|2.||World Health Organization. Meningitis in Chad, Niger and Nigeria: 2009 epidemis season. Wkly Epidemiol Rec 2010;85:57-68. |
|3.||Rajapaksa S, Starr M. Meningococcal Sepsis. Aust Fam Physician 2010;39:276-8. |
|4.||Moraes JC, Barata RB. Meningococcal disease in Sao Paulo, Brazil, in the 20 th century: epidemiological characteristics. Cad Saude Publica 2005;21:1458-71. |
|5.||Lucena R, Gomes I, Cardoso E, Goes J, Nunes L, Cardoso A, et al. Clinical and laboratory aspects of acute bacterial meningitis in infants. Arq Neuropsiquiatr 2002;60:281-4. |
|6.||Barroso DE, Carvalho DM, Casagrande ST, Rebelo MC, Soares V, Zahner V, et al. Microbiological epidemiological history of meningococcal disease in Rio de Janeiro, Brazil. Braz J Infect Dis 2010;14:242-51. |
|7.||Levy C, Taha MK, Weill Olivier C, Quinet B, Lécuyer A, Alonso JM, et al. Characteristics of meningococcal meningitis in children in France. Arch Pediatr 2008;15:105-10. |
|8.||Santos LC, Simões J, Severo M, Vazquez J, Lecour H. Bacterial Meningitis in an Urban Area: Etiologic Study and Prognostic Factors. Infection 2007;35:406-13. |
|9.||Sinclair D, Preziosi MP, John TJ, Greenwood B. The epidemiology of meningococcal disease in India. Trop Med Int Health 2010;15:1421-35. |
|10.||Safadi MA, Barros AP. Meningococcal conjugate vaccines: efficacy and new combinations. J Pediatr (Rio J) 2006;82:35-44. |
|11.||Milonovich LM. Meningococcemia: Epidemiology, Pathophysiology, and Management. J Pediatr Health Care 2007;21:75-80. |
|12.||Puricelli RC, kupek E, Bertoncini RC. Control of a community outbreak of group C meningococcal meningitis in Corupá, Santa Catarina State, Brazil, based on rapid and effective epidemiological surveillance and immunization. Cad Saude Publica 2004;20:959-67. |
|13.||Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 2007;369:2196-210. |
|14.||Escosteguy CC, Medronho Rde A, Madruga R, Dias HG, Braga RC, Azevedo OP. Epidemiologic surveillance and evaluation of meningitis hospital care. Rev Saude Publica 2004;38:657-63. |
|15.||Mantese OC, Hirano J, Santos IC, Silva VM, de Castro E. Etiological profile of bacterial meningitis in children. J Pediatr (Rio J); 2002;78:467-74. |
|16.||Donalisio MR, Rocha MM, Ramalheira RM, Kemp B. Meningococcal disease diagnostic criteria in Greater Metropolitan Campinas, Sao Paulo State, Brazil. Cad Saude Publica 2004;20:1531-7. |
|17.||Muskat M, Spiteri G, Calleja N: Invasive meningococcal disease in Malta: An epidemiological overview, 1994-2007. J Med Microbiol 2009;58:1492-8. |
|18.||Dash N, Panigrahi D, Al Khusaiby S, Al Awaidy S, Bawikar S. Acute bacterial meningitis among children <5 years of age in Oman: A retrospective study during 2000-2005. J Infect Dev Ctries 2008;2:112-5. |
|19.||Gil Prieto R, Alvarez Morán JL, Portugal P, San Román Montero J, Alvaro A, Rivero Cuadrado A. Hospital admissions for meningococcal infections in Madrid, Spain (1997-2005). Med Clin (Barc) 2010;134:534-9. |
|20.||Romanelli RM, Araújo CA, Dias MW, Boucinhas F, Carvalho IR, Martins NR, Freire HB. Etiology and evolution of bacterial meningitis in a pediatric center. J Pediatr (Rio J) 2002;78:24-30. |
|21.||Al Khorasani A, Banajeh S. Bacterial profile and clinical outcome of childhood meningitis in rural Yemen: A 2-year hospital-based study. J Infect 2006;53:228-34. |
|22.||Varon E. Epidemiology of acute bacterial meningitis in adult patients in France. Med Mal Infect 2009;39:432-44. |
|23.||Heckenberg SG, de Gans J, Brouwer MC, Weisfelt M, Piet JR, Spanjaard L, et al. Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis: A prospective cohort study. Medicine (Baltimore) 2008;87:185-92. |
|24.||Mairey E, Genovesio A, Donnadieu E, Bernard C, Jaubert F, Pinard E, et al. Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier. J Exp Med 2006;203:1939-50. |
|25.||Holub M, Beran O, Dzupová O, Hnyková J, Lacinová Z, Príhodová J, et al. Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis. Crit Care 2007;11:R41. |
|26.||Stella-Silva N, Oliveira SA, Marzochi KB. Doença meningocócica: comparaçao entre formas clínicas. Rev Soc Bras Med Trop 2007;40:304-10. |
|27.||Almeida R, Oliveira A, Cleto E, Cardoso L, Lucilia V, Morais L. Meningitis: Descriptive study of a pediatric population in the North and Center of Portugal. Rev Hosp Crianças Maria Pia 2003;12:299-308. |
|28.||Pelkonen T, Roine I, Monteiro L, Joao Simoes M, Anjos E, Pelerito A, et al. Acute childhood bacterial meningitis in Luanda, Angola. Scand J Infect Dis 2008;40:859-66. |
|29.||Daher EF, Marques CN, Lima RS, Silva Junior GB, Barbosa AS, Barbosa ES, et al. Acute kidney injury in an infectious disease intensive care unit - an assessment of prognostic factors. Swiss Med Wkly 2008;138:128-33. |
|30.||Ricciardi L, Meini M, Luchi S, Scasso A, Corbisiero R, Mencarelli M, et al. Bacterial meningitis in adults: A retrospective multicentric study in Tuscany (Italy). Infez Med 2006;14:77-84. |
|31.||Casella EB, Cypel S, Osmo AA, Okay Y, Lefèvre BH, Lichtig I, et al. Sequelae From Meningococcal Meningitis In Children: A critical analysis of dexamethasone therapy. Arq Neuropsiquiatr 2004;62:421-8. |
Elizabeth F Daher
Rua Vicente Linhares, n° 1198., CEP 60135-270. - Fortaleza, CE
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]