Meningococcal meningitis in children.

Forty-four cases of meningococcal meningitis in children at one hospital between 1971 and 1975 inclusive were studied to document the course and complications of this disease in children in the current therapeutic era. The mortality was 5%. Of the 41 survivors 76% were healthy 1 to 5 years after the episode of meningitis. Permanent severe sequelae (facial palsy, optic atrophy and ptosis) were seen in three (7%) of the survivors, and mild hearing loss, hyperactivity and nervousness were noted in seven (17%). Electroencephalography was not useful in determining management or prognosis. Both the mortality and the frequency of early and late complications among the survivors were lower than those reported from earlier studies.     

Invasive meningococcal disease associated with a very high case fatality rate in the North-West of Poland

The aim of the study was to investigate invasive meningococcal disease in the North-West of Poland, associated with a case fatality rate of 42.9%, where among the first 11 cases, eight had fatal outcome. All fatal cases were diagnosed as fulminant meningococcal severe sepsis with Waterhouse-Friderichsen syndrome and disseminated intravascular coagulation. Serotyping and pulsed-field gel electrophoresis analysis revealed that the high case fatality rate was not associated with the dissemination of one epidemic clone. However, six cases, all with good outcomes, were caused by C:2b:(P1.2,P1.5) isolates of the same pulsed-field gel electrophoresis type belonging to ST8 complex/Cluster A4.     

Effectiveness of antibiotics in preventing meningococcal disease after a case: systematic review

Objective To summarise the evidence for the role of antibiotics in preventing further cases of meningococcal disease through chemoprophylaxis given to the index patient, household contacts, and children in day care settings after a single case.Design Systematic review.Methods Studies were identified by searching Embase (1983-2003), Medline (1965-2003), and CAB Health (1973-2003) and by contacting the World Health Organization and the European meningococcal disease surveillance network and examining references of identified papers. The review included all studies with at least 10 cases in which outcomes were compared between treated and untreated groups.Main outcome measure Subsequent cases of meningococcal disease 1-30 days after onset of disease in the index patient.Results Four observational studies and one small trial met the inclusion criteria. Meta-analysis of studies on chemoprophylaxis given to household contacts showed a significant reduction in risk (risk ratio 0.11, 95% confidence interval 0.02 to 0.58). The number needed to treat to prevent a case was estimated as 218 (121 to 1135). Primary outcome data were not available in studies of chemoprophylaxis given to the index patient: when prophylaxis had not been given, rate of carriage after discharge from hospital was estimated as 3% (0 to 6), probably an underestimate of the true rate. No studies of chemoprophylaxis in day care settings were identified that met the inclusion criteria.Conclusion There have been no high quality experimental trials looking at control policies for meningococcal disease. The best available evidence is from retrospective studies. The risk of meningococcal disease in household contacts of a patient can be reduced by an estimated 89% if they take antibiotics known to eradicate meningococcal carriage. Chemoprophylaxis should be recommended for the index patient and all household contacts.     

Why Children with Severe Bacterial Infection Die: A Population–Based Study of Determinants and Consequences of Suboptimal Care with a Special Emphasis on Methodological Issues

Introduction

Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants.

Methods

A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cases to that of pediatric patients who survived a severe bacterial infection during the same period for 6 types of care: seeking medical care by parents, evaluation of sepsis signs and detection of severe disease by a physician, timing and dosage of antibiotic therapy, and timing and dosage of saline bolus. Two independent experts blinded to outcome and final diagnosis evaluated the optimality of these care types. The effect of suboptimal care on survival was analyzed by a logistic regression adjusted on confounding factors identified by a causal diagram. Determinants of suboptimal care were analyzed by multivariate multilevel logistic regression.

Results

Suboptimal care was significantly more frequent during early management of the 21 children who died as compared with the 93 survivors: 24% vs 13% (p = 0.003). The most frequent suboptimal care types were delay to seek medical care (20%), under-evaluation of severity by the physician (20%) and delayed antibiotic therapy (24%). Young age (under 1 year) was independently associated with higher risk of suboptimal care, whereas being under the care of a paediatric emergency specialist or a mobile medical unit as compared with a general practitioner was associated with reduced risk.

Conclusions

Suboptimal care in the early management of severe bacterial infection had a global independent negative effect on survival. Suboptimal care may be avoided by better training of primary care physicians in the specifics of pediatric medicine.     

Dengue deaths in Puerto Rico: lessons learned from the 2007 epidemic

Background

The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of severe dengue requires early recognition and supportive care.

Methods

Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death.

Results

Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged <15 years; 7 sought medical care at least once prior to hospital admission, 9 were admitted to hospital and 2 died upon arrival. The nine hospitalized case-patients stayed a mean of 15 hours (range: 3–48 hours) in the emergency department (ED) before inpatient admission. Five of the nine case-patients received intravenous methylprednisolone and four received non-isotonic saline while in shock. Eight case-patients died in the hospital; five had their terminal event on the inpatient ward and six died during a weekend. Dengue was listed on the death certificate in only 5 instances.

Conclusions

During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring.     

Epilepsy in the first 10 years of life: findings of the child health and education study.

OBJECTIVES--To identify children with afebrile seizures in a national cohort, classify the seizures, and document progress in the first 10 years of life. DESIGN--Population based birth cohort study. SETTING--The child health and education study, which includes 16,004 neonatal survivors (98.5% of infants born in the United Kingdom during one week of April 1970). SUBJECTS--14,676 children for whom relevant information was available. MAIN OUTCOME MEASURES--Responses to parental and general practitioner questionnaires and hospital records at 5 and 10 years after birth. RESULTS--84 children (42 boys, 42 girls) had had one or more afebrile seizure (incidence 5.7/1000). 63 children (31 boys, 32 girls) had epilepsy (incidence 4.3/1000). 49 of 55 children had a second seizure within a year of the first. The commonest seizure types were tonic-clonic (42) and complex partial (25). A greater proportion of children with complex partial seizures had recurrences. Children who had infantile spasms or a mixed seizure disorder had a poor outcome. All six children who died had symptomatic seizures in the first year, but seizures were not the direct cause of death. CONCLUSIONS--The results of this study are probably representative of seizure patterns in the general population. Outcome after seizures is determined more by the underlying disease than by the seizures themselves.     

Early treatment with parenteral penicillin in meningococcal disease.

OBJECTIVE--To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease. DESIGN--Retrospective review of hospital notes and laboratory and public health medicine department records. SETTING--Three health districts in south west England. SUBJECTS--Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381). MAIN OUTCOME MEASURE--Number of deaths from meningococcal disease. RESULTS--Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4). In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001). Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures. CONCLUSIONS--General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin. Specimens for culture should include a nasopharyngeal swab.     

Survival of 1476 patients initially resuscitated from out of hospital cardiac arrest.

OBJECTIVES--To determine the short and long term outcome of patients admitted to hospital after initially successful resuscitation from cardiac arrest out of hospital. DESIGN--Review of ambulance and hospital records. Follow up of mortality by "flagging" with the registrar general. Cox proportional hazards analysis of predictors of mortality in patients discharged alive from hospital. SETTING--Scottish Ambulance Service and acute hospitals throughout Scotland. SUBJECTS--1476 patients admitted to a hospital ward, of whom 680 (46%) were discharged alive. MAIN OUTCOME MEASURES--Survival to hospital discharge, neurological status at discharge, time to death, and cause of death after discharge. RESULTS--The median duration of hospital stay was 10 days (interquartile range 8-15) in patients discharged alive and 1 (1-4) day in those dying in hospital. Neurological status at discharge in survivors was normal or mildly impaired in 605 (89%), moderately impaired in 58 (8.5%), and severely impaired in 13 (2%); one patient was comatose. Direct discharge to home occurred in 622 (91%) cases. The 680 discharged survivors were followed up for a median of 25 (range 0-68) months. There were 176 deaths, of which 81 were sudden cardiac deaths, 55 were non-sudden cardiac deaths, and 40 were due to other causes. The product limit estimate of 4 year survival after discharge was 68%. The independent predictors of mortality on follow up were increased age, treatment for heart failure, and cardiac arrest not due to definite myocardial infarction. CONCLUSION--About 40% of initial survivors of resuscitation out of hospital are discharged home without major neurological disability. Patients at high risk of subsequent cardiac death can be identified and may benefit from further cardiological evaluation.     

Death from asthma in two regions of England

The British Thoracic Association has conducted a confidential inquiry into death from asthma of adults aged 15 to 64 years resident in the West Midland and Mersey regions in 1979. Information concerning the patients, their asthma, and death was obtained by questionnaire, interview with the general medical practitioner and a relative, and from patient records. A panel of three physicians, helped by a pathologist, identified 90 patients as dying of asthma and assessed management and treatment in the last year, last month of life, and the fatal attack. They were generally chronic asthmatics, but unstable, most having suffered severe attacks previously. Corticosteroids and bronchodilator drugs were in general underprescribed or not given in sufficiently large doses. Inhaled corticosteroids and cromoglycate had frequently not been tried. The patient''s co-operation with the management of the asthma was satisfactory for only 42 of the 90 patients. For 71 of the patients the fatal attack lasted under 24 hours; of the 77 who died at home or at work, 50 did not receive any medical attention in the fatal attack. Failure to recognise the severity of the asthma by patients, relatives, and doctor often caused delay in starting appropriate treatment. The interaction of several of these adverse factors often contributed to the patient''s death. The panel considered that there were potentially preventable factors contributory to the death of 77 (86%) of the 90 patients. Within the limits of retrospective judgment the panel considered that the routine management of the asthma was often unsatisfactory as patients known to suffer severe acute attacks were often not adequately supervised or instructed in the management and treatment of their asthma. From this retrospective inquiry we concluded that closer overall supervision, including careful attention to patient education, earlier and more intensive treatment, and pre-arranged immediate admission to hospital for asthma emergencies is desirable.     

Long term outcome of severe anaemia in Malawian children

Background

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia.

Methodology and Findings

For 18 months, we followed up children (6–60 months old) presenting to hospital with severe anaemia (haemoglobin ≤5g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p<0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075–0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003–0.015) in the combined controls (p<0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0–27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6–20.1).

Conclusions

Severe anaemia carries a high ‘hidden’ morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemia.     

Infectious disease mortality in the USSR

In recent decades infectious and parasitic diseases (class 1 according to the International Classification of Diseases-9) constitute 2-3% of causes in the total morbidity structures in the USSR. The main causes of death among diseases of class 1 are tuberculosis (37%), acute enteric infections (30%), septicemia (11%), viral hepatitides (11%), meningococcal infection (4%), measles (2%). The main groups are children aged up to 2 years (48% of fatal cases of diseases belonging to class 1). The territorial irregularity of mortality indices has been revealed.     

Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections.     

Development of renal scars in children: missed opportunities in management. South Bedfordshire Practitioners' Group.

OBJECTIVE--To assess the antecedent medical care of children with renal scars. DESIGN--Retrospective study of both general practice and hospital records. SETTING--12 Group practices in south Bedfordshire and the radiology and paediatric outpatient departments of a district general hospital. SUBJECTS--23 Children with renal scars (six boys, 17 girls) from the 12 group practices, identified from outpatient, radiology, and general practice records. MAIN OUTCOME MEASURES--Number of children in whom a diagnosis of urinary tract infection had been made without prior examination of a mid-stream specimen of urine; number of children who had had a confirmed urinary tract infection that had not been investigated further; number who had experienced delays in investigation or referral; and number who had received inadequate follow up. RESULTS--In all, 11 of the children had received suboptimal medical care, but the management of the other 12 could not have been better. The most common error was failure to investigate possible urinary tract infections, but follow up of confirmed infections was also inadequate. These problems occurred in hospital as well as in general practice. CONCLUSION--Opportunities for intervention had been missed in nearly half of this sample of children with renal scars.     

High levels of circulating cardiac proteins indicate cardiac impairment in African children with severe Plasmodium falciparum malaria

A role of the heart in the pathophysiology of severe Plasmodium falciparum malaria has recently been suggested. The objective of the present study was to substantiate this finding in a large group of African children and to correlate results with metabolic conditions in these children. Furthermore, the impact of a potential cardiac impairment on outcome in severe cases was assessed. Results may have important implications on the currently ongoing debate on fluid management in severe malaria patients. Plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), myoglobin and creatine kinase muscle-brain (CK-MB) were compared in 400 African children with severe and mild falciparum malaria. Plasma levels of these markers were correlated with lactate and glucose blood levels, indicators for hypovolemia, and with clinical outcome. Children suffering from severe malaria and children who died (n = 22) exhibited high to very high levels of cardiac markers, respectively. Cardiac factors themselves were not predictive of fatal outcome, while, in multivariate analysis, lactic acidosis was the most important biochemical predictor of death in the severe malaria group. Lactic acidosis and hypoglycemia, however, result in cardiac impairment as defined by elevated levels of circulating cardiac proteins. Our results point to hypovolemia as a major underlying cause of lactic acidosis and hypoglycemia in African children with severe falciparum malaria. These deleterious metabolic conditions contribute to myocardial affection which was evident but not predictive per se of fatal outcome.     

Meningococcal infections during infancy: confidential inquiries into 10 deaths.

The first 10 deaths from meningococcal infections in children aged under 2 years that were reported to a DHSS multicentre study were reviewed. Confidential inquiries were made of the parents, family doctors, health visitors, and hospital staff concerned with each case, and management was discussed with a paediatrician and pathologist. Diagnosis and treatment were often delayed because doctors did not realise the importance of the purpuric rash. One child died at home, and by the time they were admitted to hospital all the remaining nine were shocked and needed resuscitation. Prodromal symptoms, mainly changes in behaviour, preceded the rash in all cases. These prodromal symptoms should arouse the suspicion of septicaemia and prompt a search for petechiae so that early effective treatment may be started.     

Tuberculous meningitis in children: a retrospective study of 79 patients,with an analysis of prognostic factors.

A study of 79 cases of tuberculous meningitis in children, with an emphasis on prognostic factors, was conducted by means of a review of hospital records and completion of a follow-up questionnaire. The survival rate was 62%. Stage 3 disease (with severe changes in the sensorium and often severe neurologic abnormalities) at the time of admission, age 3 years or less, associated miliary tuberculosis and delay in the initiation of therapy correlated significantly with poor outcome. Severe neurologic complications in the acute phase were also related to poor outcome and severe sequelae. General recommendations pertaining to treatment are made.     

Recent trends in pediatric Haemophilus influenzae type B infections in Canada. Immunization Monitoring Program,Active (IMPACT) of the Canadian Paediatric Society and the Laboratory Centre for Disease Control.

OBJECTIVE: To describe changes in the number of cases of Haemophilus influenzae type b (Hib) infections among Canadian children before and after the introductory phases of Hib vaccination. DESIGN: Multicentre case series. SETTING: All 10 pediatric tertiary care centres across Canada participating in the Immunization Monitoring Program, Active (IMPACT) of the Canadian Paediatric Society and the Laboratory Centre for Disease control. PATIENTS: Children with a Hib infection admitted to any of the participating hospitals from 1985 to 1994. Annual case totals from 1985 to 1990 were determined from records of hospital laboratories or coded discharge diagnoses, or both. From 1991 to 1994 intensive case surveillance was conducted on the wards in addition to thorough record searches as above. OUTCOME MEASURES: Estimated annual case totals for 1985-90. For 1991-94 intensive surveillance for quarterly case totals, yearly age distribution of cases, and proportion of recent cases that represent vaccination failures or missed opportunities to prevent infection. RESULTS: The total number of Hib cases from 1985 to 1990 was 2095; from 1991 to 1994, there were 326 laboratory-confirmed cases and 15 probably cases supported by Hib antigen detection. The annual number of cases declined from an estimated 485 in 1985 to 24 in 1994, a decrease of 95.1%. The steepest interannual decrease (63.7%) occurred between 1992 and 1993, following the introduction of infant-based vaccination programs across Canada. The number of Hib cases involving children most at risk (those 6 to 18 months old) decreased from 78 in 1991 to 4 in 1994. Of the 24 cases in 1994, 6 were categorized as preventable, 1 was fatal, and 8 were vaccine failures (2 of which involved currently used vaccines). CONCLUSION: The prevalence of Hib infections reported by the IMPACT centres has declined greatly since the introduction of vaccination programs. However, deaths and complications continue to occur, attesting to the need to vaccinate all eligible infants and children against this virulent pathogen.     

Completeness of statutory notification for acute bacterial meningitis.

Several different sources of data, including statutory notifications, were used to identify cases of acute bacterial meningitis in childhood in a defined population. Only half the cases of meningococcal meningitis and less than one quarter of ofther types of bacterial meningitis had been notified. Notified cases differed from the remainder with respect to causative organism, age, outcome, and type of hospital of admission. Thus notifications are an unreliable measure of incidence for this disease, and studies of infectious disease based on notified cases alone should be interpreted with considerable reserve. It is suggested that infectious-disease surveillance should be both clinical and microbiological and that data from different sources need to co-ordinated. The reason for reporting each disease (or organism) should be specified and and reviewed periodically.     

Pneumococcal bacteraemia: 325 episodes diagnosed at St Thomas's Hospital.

Three hundred and twenty five episodes of pneumococcal bacteraemia occurred at St Thomas''s Hospital during 1970-84, accounting for 13.3% of all episodes of bacteraemia. Twice as many cases occurred in male as in female patients, and common predisposing factors included chronic chest disease, alcoholism, haematological malignancies, cirrhosis, and sickle cell anaemia. Mortality was 28.6% overall but only 11.8% among patients who received antibiotic treatment for at least 24 hours. Most patients (261) had pneumonia, 26 had meningitis, and eight were children with occult bacteraemia. The commonest serotype of pneumococcus in adults was type 3 (39 episodes), and these strains were associated with a high mortality. Other factors determining a fatal outcome included underlying disease (such as cirrhosis, malignancy, and chronic chest disease) and extrapulmonary infection. Almost half the survivors were treated for 10 days or less and became afebrile within 48 hours.