Meningococcal Disease In Children Research Articles

Prospective study of a real-time PCR that is highly sensitive, specific, and clinically useful for diagnosis of meningococcal disease in children.

Due to the early administration of antibiotics, meningococcal disease is increasingly difficult to diagnose by culturing. Laboratory studies have shown PCR to be sensitive and specific, but there have been few clinical studies. The objectives of this study were to determine the diagnostic accuracy and clinical usefulness of meningococcal PCR through a prospective comparison of real-time PCR, nested PCR, and standard culturing of blood and cerebrospinal fluid (CSF). The setting was a tertiary-care pediatric hospital in Australia, and the participants were 118 children admitted with possible septicemia or meningitis. The main outcome measures-sensitivity, specificity, and positive and negative predictive values-were compared to a "gold standard " fulfilling clinical and laboratory criteria. For 24 cases of meningococcal disease diagnosed by the gold standard, culturing of blood or CSF was positive for 15 (63%), nested PCR was positive for 21 (88%), and real-time PCR was positive for 23 (96%). The sensitivity, specificity, and positive and negative predictive values of real-time PCR (the most sensitive test) for all specimens were, respectively, 96% (95% confidence interval, 79 to 99%), 100% (95% confidence interval, 96 to 100%), 100% (95% confidence interval, 85 to 100%), and 99% (95% confidence interval, 94 to 100%). Of 54 patients with suspected meningococcal disease at admission, 23 had positive PCR results. Only one PCR specimen was positive in a patient thought unlikely to have meningococcal disease at admission. Blood PCR remained positive for 33% of patients tested at up to 72 h. Real-time PCR has high positive and negative predictive values in this clinical setting, with better confirmation of cases than nested PCR. Targeting patients for PCR based on admission criteria appears to be practical, and the test may remain useful for several days after the start of antibiotic administration.

Severe meningococcal disease in childhood

Severe meningococcal disease in childhood

Procalcitonin as a prognostic marker in meningococcal disease.

To assess the prognostic value of procalcitonin levels during the clinical course of meningococcal disease in children. A retrospective, descriptive study. University paediatric intensive care unit. Nine patients with meningococcal sepsis and 55 patients with meningococcal septic shock were included in the study, giving a total of 64. Procalcitonin (PCT), C-reactive protein (CRP), cytokines (IL-6, IL-8 and TNF-alpha), plasminogen activator inhibitor-1 (PAI-1) and several routine laboratory parameters were determined and expressed as medians (ranges). PCT levels on hospitalisation were elevated in all children as compared to normal values. Median PCT levels on admission were significantly higher in children with septic shock than in children with sepsis (270 ng/ml (5.7-672.3) versus 64.4 (20.6-283.7); p<0.01). When the patients were categorised to severity using the Pediatric Risk of Mortality (PRISM) score (group 1: <15 points, group 2: 16-30, group 3: >30), the PCT levels were significantly different in the three groups. All markers, with the exception of PCT (p=0.056), were significantly different between survivors and non-survivors. When the duration of petechiae was taken into account, the difference in PCT levels became significant (p=0.04). Procalcitonin levels on admission are related to severity. In the case of a short disease history (duration of petechiae), PCT levels are also related to mortality. Although PCT levels are elevated in all patients, the levels per se do not allow a prediction about survival versus non-survival, this is in contrast to other markers and scores (PRISM).

Vaccines for the prevention of meningococcal disease in children

Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae. The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135. Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children. Vaccines that protect against serogroup B disease are still in development. As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants. New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed. A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom. New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade. Copyright 2002, Elsevier Science (USA). All rights reserved.

Comparison of prediction models for adverse outcome in pediatric meningococcal disease using artificial neural network and logistic regression analyses

The objective of this study was to compare artificial neural network (ANN) and multivariable logistic regression analyses for prediction modeling of adverse outcome in pediatric meningococcal disease. We analyzed a previously constructed database of children younger than 20 years of age with meningococcal disease at four pediatric referral hospitals from 1985–1996. Patients were randomly divided into derivation and validation datasets. Adverse outcome was defined as death or limb amputation. ANN and multivariable logistic regression models were developed using the derivation set, and were tested on the validation set. Eight variables associated with adverse outcome in previous studies of meningococcal disease were considered in both the ANN and logistic regression analyses. Accuracies of these models were then compared. There were 381 patients with meningococcal disease in the database, of whom 50 had adverse outcomes. When applied to the validation data set, the sensitivities for both the ANN and logistic regressions models were 75% and the specificities were both 91%. There were no significant differences in any of the performance parameters between the two models. ANN analysis is an effective tool for developing prediction models for adverse outcome of meningococcal disease in children, and has similar accuracy as logistic regression modeling. With larger, more complete databases, and with advanced ANN algorithms, this technology may become increasingly useful for real-time prediction of patient outcome.

Treating meningococcal infections in children.

Aggressive early treatment of meningococcal disease in children can reduce mortality. This relies on prompt recognition of septicaemia and meningitis, and treatment of the complications of shock and raised intracranial pressure.

Influence of serogroup on the presentation, course, and outcome of invasive meningococcal disease in children in the Republic of Ireland, 1995-2000.

To test the hypothesis that the infecting meningococcal serogroup modulates the presentation, course, and outcome of invasive meningococcal disease (IMD), we performed a retrospective review of cases of IMD in 407 children from 2 tertiary referral centers and 2 regional centers in Ireland. Patients infected with serogroup C meningococci (n=104) were older than those infected with serogroup B (n=303; median, 2.5 vs. 1.5 years; P=.04); all other demographic and clinical parameters were similar for the 2 groups. Among serogroup B patients, mortality was 3.6% and morbidity was 10%; for serogroup C patients, mortality was 4.8% and morbidity was 12.5% (P=.81 and P=.76, respectively). Serogroup C-associated sequelae more often were multiple (P=.003). Despite the introduction of serogroup C conjugate vaccine into the routine immunization schedule of some countries, ongoing morbidity from IMD is anticipated, because group B disease was very similar to group C disease in this pediatric population.

Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism.

Critical illness outcome may be causally related to inflammatory response severity. Given that tissue angiotensin-converting-enzyme (ACE) regulates such responses and that the deletion (D) [rather than insertion (I)] variant of the ACE gene is associated with higher tissue ACE levels, DD genotype might be associated with a poorer outcome in a uniform infectious disease state. Illness severity (Pediatric RIsk of Mortality score, the Glasgow Meningococcal Septicaemia Prognostic Score [GMSPS], and clinical course) was recorded for consecutive white patients with meningococcal disease (n = 110, 34 DD genotype, 61 male, aged 49.4 +/- 5.4 months) referred to the Royal Liverpool Children's Hospital, UK. Compared with children with > or = I allele, DD genotype was associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS (DD 9.4 +/- 0.5, ID/II 7.7+/- 0.4 [mean +/- SEM], p = 0.013), greater prevalence of inotropic support (76% versus 55%, p = 0.03) and ventilation (82% versus 63%, p = 0.04), and longer Pediatric Intensive Care Unit (PICU) stay (5.8 versus 3.9, p = 0.02). DD genotype frequency was 6% (1 case) for the 18 children who did not require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p = 0.01). ACE DD is associated with increased illness severity in meningococcal disease.

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash

Background: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier...

Macrophage migration inhibitory factor in meningococcal disease in children

Macrophage migration inhibitory factor in meningococcal disease in children

Parental smoking, socioeconomic factors, and risk of invasive meningococcal disease in children: a population based case-control study

AIMSTo investigate the effects of parental smoking, socioeconomic characteristics, and indoor environment on the risk of invasive meningococcal disease in children.METHODSPopulation based case-control study. A total of 68 incident cases...

Temporal association of chickenpox and meningococcal disease in children: a report of three cases

Temporal association of chickenpox and meningococcal disease in children: a report of three cases

Improving the outcome of septic shock in children.

Sepsis is an important cause of pediatric morbidity and mortality. Improving the outcome of pediatric sepsis requires diverse efforts, including prevention, early recognition, improvements in early management and transport, and physiology-directed care. Awareness that septic shock represents a pathophysiologic host response to infection has prompted investigation of immune mediators and coagulation factors as potential targets for anti-sepsis therapies. Advancements thus far include: the potential prevention of neonatal sepsis with granulocyte colony-stimulating factor; recognition of clindamycin as a potential inhibitor of endotoxin release; improved outcome from meningococcal disease in children treated with bactericidal/permeability-increasing protein (rBPI21); and improved outcome from sepsis in premature infants treated with pentoxifylline. Further randomized controlled studies of immunomodulatory agents are indicated and a few are in progress. Current studies on genetic propensities in cytokine and coagulation protein expression may explain variability in patient outcomes and eventually lead to genomics-based therapeutics.

Temporal association of chickenpox and meningococcal disease in children: a report of three cases

Temporal association of chickenpox and meningococcal disease in children: a report of three cases

Frequency of myocarditis in cases of fatal meningococcal infection in children: observations on 31 cases studied at autopsy.

The frequency of myocarditis associated with meningococcal disease in children was reported only in two autopsied series (United States and South Africa). Here we report the frequency of associated myocarditis in 31 children who died of meningococcal infection at Hospital Infantile N.S. da Glória in Vitória, Espirito Santo State, Brazil. The diagnosis was confirmed by isolation of Neisseria meningitidis. At least three sections of fragments of both atria and ventricles were studied using the Dallas Criteria for the morphologic diagnosis of myocarditis. The mean age was 47.6 +/- 39.8 months and the mean survival time after the onset of symptoms was 46.1 +/- 26.5 h (12-112 h). Myocarditis was present in 13 (41.9%) patients, being of minimal severity in 11 cases and of moderate severity in 2 cases. There were no cases with severe diffuse myocarditis. The frequency of myocarditis was not influenced by sex, presence of meningitis, survival time after the onset of symptoms or use of vasoactive drugs. The frequency of myocarditis reported here was intermediate between the values reported in the only two case series published in the literature (57% in the United States and 27% in South Africa). Although our data confirm the high frequency of myocarditis in meningococcal disease, further investigations are necessary to elucidate the contribution of myocarditis to myocardial dysfunction observed in cases of meningococcal infection in children.

Cerebrospinal fluid pleocytosis and prognosis in invasive meningococcal disease in children.

The absence of cerebrospinal fluid (CSF) pleocytosis in invasive meningococcal disease (IMD) has been associated with an increased risk of death. It is unknown whether patients who lack a cellular response to central nervous system (CNS) infection are at the same risk of adverse outcome as patients who lack CNS infection. To determine the frequency of presentation and outcome of three groups of children with IMD: Group 1, children with CSF pleocytosis; Group 2, children without CSF pleocytosis and with negative CSF cultures (bacteremia alone); and Group 3, children without CSF pleocytosis but with positive CSF cultures (CNS infection without CSF pleocytosis). We reviewed the medical records of children with IMD at four pediatric referral hospitals between 1985 and 1996. Clinical and laboratory indices and severe adverse outcomes (defined as death or limb loss) were compared in the three groups. Multivariable logistic regression analysis was performed to determine whether CNS infection without CSF pleocytosis was independently associated with adverse outcome in IMD. Three hundred seventy-seven children with IMD were identified. Eighty-six patients were excluded because their CSF analysis either was not done or was unevaluable; of these patients 22 (25.6%) had an adverse outcome. Of the 291 evaluable patients 204 (70.1%) had CSF pleocytosis, 52 (17.9%) had bacteremia alone and 35 (12.0%) had CNS infection without CSF pleocytosis. Patients with CNS infection without CSF pleocytosis had significantly lower white blood cell and platelet counts and more coagulopathy than patients with bacteremia alone (P < or = 0.05) or patients with CSF pleocytosis (P < or = 0.01). The frequency of adverse outcome was 40% for patients with CNS infection without CSF pleocytosis compared with 9.6% for patients with bacteremia alone (P = 0.001) and 3.4% for patients with CSF pleocytosis (P < 0.001). CNS infection without CSF pleocytosis was independently associated with adverse outcome by multivariable logistic regression analysis (P = 0.003). Approximately 30% of all children with IMD present without CSF pleocytosis. Of these patients those with CNS infection without pleocytosis are at higher risk of adverse outcome than either patients with CSF pleocytosis or patients with bacteremia alone.

Tobacco smoke as a risk factor for meningococcal disease

Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Who spots the spots? Diagnosis and treatment of early meningococcal disease in children.

Meningococcal disease can begin suddenly and may kill within hours.1 Delays in diagnosis and treatment can therefore decrease the chances of survival. The commonest delays in those who die are: parents not recognising that their child is seriously ill; and doctors failing to make a correct diagnosis.2 Information for parents and doctors about meningococcal disease should emphasise the septicaemic rash, not meningitis Accurate information about meningococcal disease for both parents and doctors is therefore extremely important. The information widely available, however, may be misleading, because it tends to focus on meningitis rather than on septicaemia.3 More deaths result from septicaemia, and the proportion of children who present with septicaemia is increasing.4 We conducted a prospective study of children admitted with meningococcal disease over a period of 18 months, and we highlight the details of one case in which a missed diagnosis led to the child's death. This prospective study included all children admitted with meningococcal disease over 18 months to four hospitals in Merseyside: Alder Hey Children's Hospital, Arrowe Park, Whiston Hospital, and the Countess of Chester Hospital. Parents were interviewed on admission and were asked about specific features they had noticed, their reasons for seeking medical advice, and the outcome of any contact with a doctor during the illness. One hundred and twenty six children with meningococcal disease were admitted, 13 of whom died. Neisseria meningitidis was isolated from 78 cases. The median age (range) was 20 months (3 months to 14 years). On admission 113 children had a …

Multivariable predictive models for adverse outcome of invasive meningococcal disease in children

For prediction of adverse outcome (AO, defined as death or limb amputation) of invasive meningococcal disease (IMD) in children, two multivariable models were derived and validated by reviewing the data in the medical records of patients with IMD, who ranged from birth to 19 years of age, at three pediatric referral hospitals between 1985 and 1990 (derivation set, n = 153, 19 AO) and between 1991 and 1994 (validation set, n = 92, 11 AO). Variables in the derivation set significantly associated with AO ( p <0.05) were entered into a logistic regression analysis. Because coagulation studies (prothrombin time, partial thromboplastin time, and serum fibrinogen concentration) were available for only 50% of patients, two analyses were performed, either excluding (model 1) or including (model 2) coagulation studies. These analyses identified an absolute neutrophil count less than 3000/mm 3, poor perfusion, and a platelet count less than 150,000/mm 3 (model 1), and a serum fibrinogen concentration less than 2.5 gm/L (250 mg/dl) and an absolute neutrophil count less than 3000/mm 3 (model 2), as independent predictors of AO ( p <0.05). When the models were tested on the validation set, the presence of at least two of the three predictors in model 1 had a sensitivity of 82% and a specificity of 97% in predicting AO; the presence of both predictors in model 2 had a sensitivity of 89% and a specificity of 97%. These models can reliably identify patients with IMD at high risk of AO for whom consideration of novel therapies is justified. (J Pediatr 1996;129:702-10)

Meningococcal disease in childhood—a regional study in Ireland

A retrospective study of microbiology laboratory records of culture-confirmed cases of meningococcal disease in children under 14 years of age, admitted to four Dublin hospitals, was conducted for the period 1981-1991 inclusive. The study aimed to describe the epidemiology of meningococcal disease in childhood and to assess the potential of meningococcal group A and C vaccine in preventing disease. There were 406 cases of meningococcal disease of which 319 (78.6%) were in children under 5 years of age. The meningitis to septicaemia ratio was almost 4:1 (320 vs. 86 cases). Of the 406 cases, 216 (53.2%) cases occurred during the period November to March. The age-specific annual incidence rates for the Eastern Health Board region served was 64.2 per 100,000 under 1 year of age and 24.6 per 100,000 under 5 years of age. A relative increase in disease caused by meningococcal serogroup C was observed during the period of the study. Only 15% all cases could have been prevented by a policy of universal meningococcal group A and C immunisation at 2 years of age. Such a policy, therefore, is not recommended. A vaccine for preventing disease caused by meningococcal group B is urgently required.