Changing Patterns of Disease and Mortality at the Children’s Hospital,Accra: Are Infections Rising?

BackgroundThe Millennium Development Goals (MDGs) have led to reductions in child mortality world-wide. This has, invariably, led to the changes in the epidemiology of diseases associated with child mortality. Although facility based data do not capture all deaths, they provide an opportunity to confirm diagnoses and insight into these changes which are relevant for further disease control.ObjectiveTo identify changes in the disease pattern of children who died at the Princess Marie Louise Children’s Hospital (PML) in Ghana from 2003–2013.MethodsA cross sectional review of mortality data was carried out at PML. The age, sex, duration of admission and diagnosis of consecutive patients who died at the hospital between 2003 and 2013 were reviewed. This information was entered into an Access database and analysed using Stata 11.0 software.ResultsAltogether, 1314 deaths (3.6%) occurred out of a total of 37,012 admissions. The majority of the deaths, 1187 (90.3%), occurred in children under the age of 5 years. While deaths caused by malaria, malnutrition, HIV infection and diarrhoea decreased, deaths caused by pneumonia were rising. Suspected septicaemia and meningitis showed a fluctuating trend with only a modest decrease between 2012 and 2013. The ten leading causes of mortality among under-fives were malnutrition, 363 (30.6%); septicaemia, 301 (25.4%); pneumonia, 218 (18.4%); HIV infection, 183 (15.4%); malaria, 155 (13.1%); anaemia, 135 (11.4%); gastroenteritis/dehydration, 110 (9.3%); meningitis, 58 (4.9%); tuberculosis, 34 (2.9%) and hypoglycaemia, 27 (2.3%). For children aged 5–9 years, the leading causes of mortality were malaria, 42 (42.9%); HIV infection, 27 (27.6%); anaemia, 14 (14.3%); septicaemia, 12 (12.2%); meningitis, 10 (10.2%); malnutrition, 9 (9.2%); tuberculosis, 5 (5.1%); pneumonia, 4 (4.1%); encephalopathy, 3 (3.1%); typhoid fever, 3 (3.1%) and lymphoma, 3 (3.1%). In the adolescent age group, malaria, 8 (27.6%); anaemia, 6 (20.7%); HIV infection, 5 (17.2%); sickle cell disease, 3 (10.3%) and meningitis, 3 (10.3%) were most common.ConclusionThere has been a decline in the under-five mortality at PML over the years; however, deaths caused by pneumonia appear to be rising. This highlights the need for better diagnostic services, wider HIV screening and clinical audits to improve outcomes in order to achieve further reductions in child mortality and maintain the gains.     

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.     

Gene expression in cortex and hippocampus during acute pneumococcal meningitis

Background  

Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.     

Surveillance of Haemophilus influenzae serotypes and antimicrobial resistance in Colombia, 1994-2002

Invasive disease caused by Haemophilus influenzae serotype b results in high rates of morbidity and mortality among children. In 1994, the Microbiology Group at the Instituto Nacional de Salud (Colombia) initiated a program to detect antimicrobial resistance in H. influenzae. Invasive isolates were collected by hospitals and public health laboratories as part of surveillance programs for acute respiratory infections and acute bacterial meningitis. To determine the evolution of serotypes and antimicrobial resistance patterns, invasive H. influenzae isolates collected from 1994 to 2002 were compared, and the impact of Hib conjugated vaccine in Colombia was reassessed. The analysis included 683 isolates, 379 (55.5%) were recovered from male patients, 370 (54.2%) from children under one year, 227 (33.2%) from children aged 1 to 5, 19 (2.8%) from children aged 6 to 14, and 38 (5.6%) from children over 14 years; 29 (4.2%) with no age data. Clinical classification recorded 493 (72.2%) of the samples were from patients with meningitis, 181 (26.5%) with pneumonia, and 9 (0.9%) with other diseases. Eighty five percent of isolates corresponded to H. influenzae serotype b, 12.9% were non capsular, and 2.0% corresponded to other serotypes (10 a, 1 d, 1 e and 2 f). Of the total number of isolates, 12.0% produced beta lactamase, 13.9% were resistant to ampicillin, 12.7% to trimethoprim sulfamethoxazole (SXT), 5.4% to chloramphenicol, 1% to cefuroxime. All isolates were susceptible to ceftriaxone. During the 10-year period, resistance to SXT increased from 5% to 13%. A significant decrease in meningitis cases was detected among children under one-year old and in the 1 to 5 age group. Before introducing the vaccine, an annual average of 43 and 23 isolates for each of these groups were received. During 2002, 10 and 6 isolates, respectively, were received for each group. Surveillance of invasive H. influenzae isolates has allowed the evaluation of Hib vaccine impact, as well as the detection of an increase of non-capsular isolates, and changes in resistance patterns.     

Neuroinfections due to Enterococcus faecalis in children

Enterococcal meningitis is a rare complication of neurosurgical procedure or high technology treatment of children and occurs mainly imunocompromised neonates with very low birth weight, severe prematurity and complicates sometime ventriculoperitoneal shunt insertion or perinatal trauma. E. faecalis caused 10 nosocomial meningitis and all strains were susceptible to vancomycin and chloramphenicol, and in our database 90% also to gentamicin and ampicillin. Mortality in our group of 10 children was 20% what is insignificantly higher than overall mortality in the whole cohort of meningitis within last 15 years in our database (15.1%). Early empiric therapy should include also ampicillin or vancomycin, if enterococcal etiology is suspected.     

结核性脑膜炎的诊断和治疗

结核性脑膜炎(TBM)是一种严重的肺外结核性,约占全部结核病的1%。TBM的死亡率和致残率高,至今仍是发展中国家最严重的疾病之一。儿童患者及合并HIV感染的结核性脑膜炎患者死亡率明显增高。结核性脑膜炎的具体发病机制仍不清楚,细菌和宿主的遗传因素在结脑的发病机制中发挥了至关重要的作用。尽管现代医学技术的进展,TBM的早期诊断仍存在困难。TBM的诊断依赖于临床表现、实验室检查以及影像学检查,脑脊液细菌涂片或培养找到结核分枝杆菌可确诊。早期诊断和治疗尤为关键。临床上往往从经验判断开始抗结核治疗。WHO指南推荐至少六个月的抗结核治疗。然而,部分指南推荐延长抗结核治疗至9-12个月。早期使用类固醇类激素可降低死亡率。抗结核药物耐药性与高死亡率相关。该综述描述了结脑的各个方面,重点强调结核性脑膜炎的早期诊断和治疗。     

76例儿童隐球菌性脑膜炎临床分析

目的分析儿童隐球菌性脑膜炎临床特点。方法回顾性分析76例隐球菌性脑膜炎患儿临床资料。结果男47例,女29例,平均年龄(6.34±3.67)岁;主要临床表现为发热(100%)、头痛(78.95%)、呕吐(81.58%);首次脑脊液墨汁染色阳性46例(60.53%),首次脑脊液真菌培养阳性21例(27.63%),两性霉素B联合5-氟胞嘧啶抗真菌治疗好转率(74.19%),两性霉素B联合氟康唑治疗好转率(62.96%),差异无统计学意义(P=0.75)。结论儿童隐球菌性脑膜炎极易误诊、漏诊,反复、多次腰穿有助于早期诊断;两性霉素B联合5-氟胞嘧啶是抗真菌治疗首选方案,早期诊断、积极降颅压是改善预后的关键。     

High Mortality amongst Adolescents and Adults with Bacterial Meningitis in Sub-Saharan Africa: An Analysis of 715 Cases from Malawi

Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.

Methods

We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm³ (>50% neutrophils) in HIV negative participants and >5 cells/mm³ in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).

Results

Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.     

Bacterial meningitis after craniocerebral trauma in the community

Craniocerebral trauma is one of major risk factors for development of meningitis. We reviewed 30 cases of bacterial meningitis occurring in community after craniocerebral trauma. Alcohol abuse was significant risk factor occurring in trauma patients with meningitis present in 50% in our cohort (p=0.0001). The most common pathogen in posttraumatic meningitis was Str. pneumoniae (90% vs. 33.8%, p=0.0001). However mortality was very low, only 5% probably because of early diagnosis and treatment of patients at risk for bacterial meningitis but neurologic sequellea were significantly more common (p=0.00001) in patients after craniocerebral trauma.     

Neurological Complications after Neonatal Bacteremia: The Clinical Characteristics,Risk Factors,and Outcomes

Background

Neonates with bacteremia are at risk of neurologic complications. Relevant information warrants further elucidation.

Study Design

This was a retrospective cohort study of neonates with bacteremia-related neurologic complications (BNCs) in a tertiary-level neonatal intensive care unit (NICU). A systemic chart review was performed conducted to identify clinical characteristics and outcomes. A cohort of related conditions was constructed as the control group. Logistic regression analysis was used to identify independent risk factors for BNC.

Results

Of 1037 bacteremia episodes, 36 (3.5%) had BNCs. Twenty-four cases of BNCs were related to meningitis, five were presumed meningitis, and seven occurred after septic shock. The most common causative pathogens were Group B streptococcus (41.7%) and E. coli (16.7%). The major BNCs consisted of seizures (28), hydrocephalus (20), encephalomalacia (11), cerebral infarction (7), subdural empyema (6), ventriculitis (8), and abscess (4). Eight (22.8%) neonates died and six (16.7%) were discharged in critical condition when the family withdrew life-sustaining treatment. Among the 22 survivors, eight had neurologic sequelae upon discharge. After multivariate logistic regression analysis, neonates with meningitis caused by Group B streptococcus (adjusted odds ratio [OR]: 8.90, 95% confidence interval [CI]: 2.20–36.08; p = 0.002) and combined meningitis and septic shock (OR, 5.94; 95% CI: 1.53–23.15; p = 0.010) were independently associated with BNCs.

Conclusions

Neonates with bacteremia-related neurologic complications are associated with adverse outcomes or sequelae. Better strategies aimed at early detection and reducing the emergence of neurologic complications and aggressive treatment of Group B streptococcus sepsis are needed in neonates with meningitis and septic shock.     

Haemophilus influenzae meningitis in Manitoba and the Keewatin District,NWT: potential for mass vaccination.

A community-based surveillance study of all central nervous system infections was carried out in Manitoba and the Keewatin District, NWT, between Apr. 1, 1981, and Mar. 31, 1984. There were 201 cases of bacterial meningitis in Manitoba over the study period, 81 (40%) caused by Haemophilus influenzae; all but one isolate tested were type b (Hib). There were nine cases of H. influenzae meningitis in the Keewatin District. The overall annual incidence rate of H. influenzae meningitis in Manitoba was 2.5/100,000; for children under 5 years the rate was 32.1/100,000. For the Keewatin District the corresponding rates were 69.6/100,000 and 530/100,000. A total of 85% and 100% of the cases of H. influenzae meningitis occurred by 24 months of age in Manitoba and the Keewatin District respectively. The age at onset was earlier in native Indian children (22 cases) and Inuit children (9 cases) than in non-native children (59 cases) (p less than 0.005); thus, vaccine prevention of Hib meningitis will likely be more difficult in native Indian and Métis children. Without evaluating the increased potential of H. influenzae vaccines to prevent nonmeningitic forms of disease, we concluded that mass childhood vaccination with polyribosylribitolphosphate (PRP) vaccine is not warranted in Manitoba or the Keewatin District. Immunogenicity studies suggest that administration of conjugated Hib vaccines such as PRP-D in infancy may prevent approximately one-third to two-thirds of cases of H. influenzae meningitis; these vaccines warrant consideration for use in mass childhood vaccination programs.     

The utility of the polymerase chain reaction assay for aetiologic definition of unspecified bacterial meningitis cases

Most patients with acute suppurative meningitis are otherwise healthy individuals with regard to immune mechanisms against invasive bacterial disease. This medical emergency is among the most dramatic and potentially ravaging diseases that affect humans, particularly young children. The illness often strikes suddenly, and can either result in death or leave the survivors with significant neurological dysfunctions. The demonstration of a bacterial aetiology is necessary for decisions regarding treatment and prophylaxis. Conventional bacteriological methods frequently fail to identify an agent, as a result of administration of antibiotics or delayed lumbar punctures. We investigated the major aetiologic sources of unspecified bacterial meningitis cases (G00.9, ISCD-10) by polymerase chain reaction (PCR)-based identification of Neisseria meningitidis (crgA), Streptococcus pneumoniae (ply) and Haemophilus influenzae (bexA) in cerebrospinal fluid samples. The multiplex PCR detected N. meningitidis in 92%, S. pneumoniae in 4% and H. influenzae in 1% of the 192 clinical samples assayed; 3% were negative for all three DNA targets. Bacterial DNA detection was found to be a valuable adjunct to enhance bacterial meningitis surveillance when the yield of specimens by culture is reduced. The implementation of PCR assays as a diagnostic procedure in Public Health Laboratories is perceived to be a significant advance in the investigation of bacterial meningitis.     

Gram-negative bacillary community acquired meningitis is not a rare entity in last two decades

The aim of this short note is to assess gram-negative bacillary community acquired meningitis (CBM) and nosocomial meningitis (NM) within 17 years nationwide survey. All cases of gram-negative bacillary CBM within 1990-2007 were assessed in national database of 372 patients with bacterial meningitis: 69 of gram-negative cases were nosocomial and 24 of gram-negative meningitis cases were CBM. Those 24 cases were compared with all CBM (201 cases) for risk factors and outcome. Among nosocomial gram-negative pathogens, A. baumannii in 23 cases, Ps. aeruginosa in 15 cases and Enterobacteriaceae in 31 cases were isolated. Among CBM, in 13 cases Enterobacteriaceae (Escherichia coli 6, Klebsiella pneumoniae 3, Proteus mirabilis 2, Enterobacter cloacae 2), in 5 cases Ps. aeruginosa and in 6 cases Acinetobacter baumannii were isolated from cerebrospinal fluid (CSF). The only significant risk factor for CBM due to gram-negative bacilli was neonatal age (12.5% vs. 3.5%, p=0.04) as underlying disease. However, mortality among gram-negative bacillary meningitis was significantly higher (12.4% vs. 37.5%, p=0.001) in comparison to other meningitis.     

Nosocomial meningitis caused by Enterobacteriaceae: risk factors and outcome in 18 cases in 1992-2007

Nosocomial neuroinfections due to Enterobacteriaceae represented 9.5% in our cohort of 171 cases of paediatric meningitis within last 15 years. Commonest etiologic agents was E. coli - 9 (50%) followed by Klebsiella pneumoniae - 3 (16,7%) and Enterobacter cloacae. Citrobacter freundii, Proteus mirabilis and Salmonella enteritidis (1 each). Commonest risk factors were neonatal age 13 - (72.2%), very low birth weight 5 (27.8%), craniocerebral trauma - 4 (22.2%) and neurosurgery - 5 (27.8%). All but 1 case were treated with antibiotics: 8 with III-rd and 3 with IV-th generation cephalosporins (ceftazidim, cefotaxim and cefepim) 2 with meropenem and 4 with ciprofloxacin: Nosocomial meningitis due to enterobacteriaceae was associated with significantly high mortality (29.9% vs. 15.1% in all cohort of pediatric meningitis - p<0.02).     

LOW PROFILE BIOPROSTHESIS FOR CARDIAC VALVE REPLACEMENT: EARLY CLINICAL RESULTS

Between May 1976 and April 1977, 100 patients underwent cardiac valve replacement with a unique low profile glutaraldehyde-treated porcine aortic xenograft. These patients were classified in four groups: Group I, 43 patients who underwent isolated mitral valve replacement (MVR); Group II, 27 patients who had isolated aortic valve replacement (AVR); Group III, 10 patients who had MVR and AVR; and Group IV, 20 patients who had MVR or AVR associated with other cardiac procedures. The operative mortality for Group I was 2.3% (1 of 43) and 15% (3 of 20) in Group IV. The total operative mortality was 4% (4 of 100) and the late mortality was 1.02% (1 of 96 survivors), who died apparently secondary to a cardiac arrhythmia. During a follow-up period extending for 16 months, thromboembolic complications occurred early in the postoperative period in 3% (3 of 100), one patient with neurological residual, and two patients with transient symptoms only. The embolic complications occurred only in Group I. Considering all patients in whom the mitral valves were replaced, the incidence of emboli was 4.9% (3 of 61). The 96 patients did not receive anticoagulant therapy. Reoperation was necessary in one patient because of periprosthetic leak. The incidence of endocarditis was 1.02% (1 of 96 survivors). We recommend anticoagulant therapy for eight to twelve weeks postoperatively in MVR patients after bioprosthetic insertion.     

Haemophillus influenzae community acquired meningitis occurrence in children despite 10 years vaccination

Despite of 10 years vaccination of all children within 1st year in Slovakia against H. influenzae, this severe infection still occurs. Among 201 cases of community acquired bacterial meningitis, 14 (7%) were caused by H. influenzae serotype B. Outcome however, after early institution of treatment was fortunately positive - only 1 patient died (7.1% mortality) and in 2 other neurologic sequellae occurred (14.3%), which were transient and mild.     

脑脊液乳酸和血清降钙素原及C反应蛋白对小儿细菌性脑膜炎的诊断价值

目的 探讨脑脊液乳酸、血清降钙素原及C反应蛋白对小儿细菌性脑膜炎的诊断价值。方法 选取我院2016年4月至2017年6月收治的50例细菌性脑膜炎患儿以及50例病毒性脑膜炎患儿进行作为研究对象,比较2类患儿脑脊液乳酸（LA）、血清降钙素原（PCT）及C反应蛋白（CRP）的水平,并分析其诊断价值。结果 细菌性脑膜炎组患儿脑脊液LA、血清PCT及CRP水平显著高于病毒性脑膜炎患儿（均P<0.05）。血清PCT诊断的灵敏度和特异度最高（96.4%、90.9%,P<0.05）。3项指标联合检测的灵敏度（100.0%）和特异度（95.5%）明显高于任一单项指标（均P<0.05）。经过Pearson相关性分析,脑脊液LA、血清PCT及CRP与小儿细菌性脑膜炎均呈显著正相关关系（均P<0.05）。结论 脑脊液乳酸、血清PCT及CRP对小儿细菌性脑膜炎的诊断和治疗效果监测有重要应用价值。     

Haemophilus influenzae type B meningitis: a contagious disease of children.

The families of 126 consecutive patients with Haemophilus influenzae type B meningitis were surveyed for secondary invasive H influenzae disease among household contacts. A total of 120 of the families were contacted. In six cases no contact was possible and the medical record was reviewed. Some 555 household contacts were found; 31% (171) were under 5 years of age. A secondary case was defined as a household contact with H influenzae type B isolated from blood or cerebrospinal fluid more than 24 hours, but less than 30 days, after admission to hospital of the index case. Four secondary cases were identified, all in children aged under 5 years. The secondary attack rate in children under 5 years or less in the month after exposure to an index case was thus 2.3%, 800 times the endemic attack rate for H influenzae meningitis. This is a conservative estimate since five additional contact cases were documented, but not included in the secondary attack rate. Young contacts of a child with H influenzae meningitis are thus at significant risk of life-threatening secondary disease.     

Meningitis in infancy in England and Wales: follow up at age 5 years

ObjectiveTo describe important sequelae occurring among a cohort of children aged 5 years who had had meningitis during the first year of life and who had been identified by a prospective national study of meningitis in infancy in England and Wales between 1985 and 1987.DesignFollow up questionnaires asking about the children''s health and development were sent to general practitioners and parents of the children and to parents of matched controls. The organism that caused the infection and age at infection were also recorded.SettingEngland and Wales.ParticipantsGeneral practitioners and parents of children who had had meningitis before the age of 1 year and of matched controls.ResultsAltogether, 1584 of 1717 (92.2%) children who had had meningitis and 1391 of 1485 (93.6%) controls were successfully followed up. Among children who survived to age 5 years 247 of 1584 (15.6%) had a disability; there was a 10-fold increase in the risk of severe or moderate disability at 5 years of age among children who had had meningitis (relative risk 10.3, 95% confidence interval 6.7 to 16.0, P<0.001). There was considerable variation in the rates of severe or moderate disability in children infected with different organisms.ConclusionThe long term consequences of having meningitis during the first year of life are significant: 32 of 1717 (1.8%) children died within five years. Not only did almost a fifth of children with meningitis have a permanent, severe or moderately severe disability, but subtle deficits were also more prevalent.

What is already known on this topic

Meningitis in infancy is associated with important long term consequencesThere is considerable variation in outcome depending on which organism caused the infection

What this study adds

This follow up study of 1717 children who had meningitis in infancy found that they had a 10-fold increase in risk of severe or moderate disabilities at age 5 years compared with children in the control groupThe outcome of having meningitis was associated with the age at infection, and children who had meningitis in the neonatal period were more likely to have health and development problems than those older than 1 monthSubtle deficits, such as middle ear disease and visual and behavioural problems, were more prevalent among children who had had meningitis in infancy     

Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study.

OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION--The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves.