Hearing in children after meningococcal meningitis

OBJECTIVE: To review the outcome of sensorineural hearing loss in children who have had confirmed meningococcal meningitis. METHODS: A retrospective audit of children admitted to the Starship Children's Hospital with a confirmed diagnosis of meningococcal meningitis during a 4-year period. RESULTS: Sixty-five children had confirmed meningococcal meningitis. Dexamethasone was administered according to recommended guidelines in 46 children (72%) while 12 children (19%) did not receive steroids at any stage. All children were appropriately referred for hearing assessment. Forty-nine children (75%) had their hearing tested and reliable sensorineural evaluation was obtained in all but one case. Thirty-four children (70%) were seen up to 6 weeks from discharge, 86% by 12 weeks. Sixteen cases (25%) did not attend for audiological assessment. Sensorineural hearing impairment was found in two children (4.2%). CONCLUSIONS: Children with meningococcal meningitis were reliably referred for audiological assessment but 39% either failed to attend for an outpatient hearing evaluation (25%) or had an unacceptable delay between discharge and testing (14%). Of those reliably tested, two children (4.2%) had significant sensorineural hearing loss.     

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp(299)Gly and Thr(399)Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.     

Clinical data in children with meningococcal meningitis in a Spanish hospital

Neisseria meningitidis is the main cause of bacterial meningitis in Spain. Of the 213 children included in this study with meningococcal meningitis, 7 died. Mortality was linked to a shorter time from the first symptom to diagnosis (mean time for fatal cases was 9.5 h, mean time for survivors was 19h, p = 0.034), to deteriorated consciousness (DC) (mortality rate (MR) with DC = 6/87, MR without DC = 1/124, p = 0.02) and to shock (MR with shock = 5/7, MR without shock = 2/206, p < 0.0001). Previous treatment reduced the yield from blood culture (36/54 versus 45/137, p < 0.0001). Positivity in both Gram stain (GS) and cerebrospinal fluid (CSF) culture increased with longer duration of symptoms (mean GS+= 25h, GS^-= 16h, p = 0.004; CSF+= 20h, CSF^-= 12h, p = 0.001), and blood culture (BC) gave more positive results when carried out earlier (mean BC+= 14 h, BC = 24 h, p < 0.001). Reduced susceptibility to penicillin was seen in 34% of the strains, and rapidly evolving forms were responsible for most of the deaths; reduced susceptibility was more frequent among strains responsible for death or sequelae (9/15 = 60%) as compared with the more harmless strains (69/ 215 = 32%) ( p = 0.04). The progressive reduction of susceptibility to penicillin indicates that it should be replaced by a third-generation cephalosporine.     

A toll-like receptor 4 variant is associated with fatal outcome in children with invasive meningococcal disease

Aims: Toll-like receptor 4 (TLR4) is the major endotoxin signalling receptor of the innate immune system and is required for efficient recognition of bacterial infections. Here, we analysed a possible association between the TLR4 variant Asp299Gly and disease outcome in children with invasive meningococcal disease.
Methods: In total, 197 children with invasive meningococcal disease were analysed for the TLR4 Asp299Gly variant. Genotyping results were correlated with mortality, the frequency of ventilation support, application of inotropic substances, skin grafting, and limb loss.
Results: The overall Asp299Gly allele frequency was 9.4%. Detection of a heterozygous Asp299Gly TLR4 mutation was significantly associated with fatal outcome (non-survivor group: 31.6% vs. survivor group: 12.1%; p = 0.021) and was even more pronounced in patients with disease onset less than 24 months of age (non-survivor group: 42.8% vs. survivor group: 10.2%; p = 0.006). In this age group, ventilation support was also more frequent in patients with the Asp299Gly genotype (37.5% vs. 6.2%).
Conclusion: Our data suggest that the heterozygous TLR4 Asp299Gly genotype is associated with an increased mortality in children with invasive meningococcal disease.     

Clinical features and complications of epidemic group A meningococcal disease in Sudanese children.

The clinical presentation and laboratory features in relation to short-term outcome in 118 prospectively studied Sudanese children who were admitted with meningococcal (MC) meningitis and/or septicaemia during the 1988 group A MC epidemic in Greater Khartoum are described. Their ages ranged from 25 days to 15 years (mean: 78 months) and 42% were less than 5 years old. The male:female ratio was 1.6:1. Forty (34%) came from one of the peri-urban shanty towns encircling Greater Khartoum. A history of MC immunization (A and C vaccine) was obtained in 22%, but only five children (4.8%) had the vaccine between 4 weeks and 1 year before their illness. The commonest symptoms on admission were vomiting, neck rigidity and diarrhoea. Convulsions were significantly more frequent in children under 5 years old (p = 0.0005). Fifty-six (47%) had evidence of malnutrition. In descending order, fever, neck stiffness and Kernig's sign were the most commonly observed signs, the latter two being significantly more often detected in children older than 1 year. Twenty-four patients 20%) had disturbed consciousness. The case fatality rate was 6.3% and this was significantly higher in those presenting with meningococcal septicaemia (p = 0.0006). Other significant associations with mortality were short duration (less than 1 day) of symptoms (p = 0.0006) and clinical shock detected on admission p = 0.003). Transient complications were infrequent and permanent neurological sequelae were confined to bilateral profound sensorineural hearing loss in three children (2.9%) and hemiplegia in two 1.9%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of group A and group C meningococcal infection

114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded.     

Comparative study of group A and group C meningococcal infection.

114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded.     

Fc gamma receptor allotypes in children with bacterial meningitis. A preliminary study

IgG2 antibody is the essential subclass to protect against encapsulated bacteria Fc gamma RIIa is the only Fc gamma receptor that interacts with human IgG2. The two genetically determined allotypes of human Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131 alleles have functionally different reactivities with IgG2 in vitro, and H/H-131 cells have markedly higher binding affinity for human IgG2. Homozygous Fc gamma RIIIb-NA1/NA1 PMNLs show higher phagocytic capacity than Fc gamma RIIIb-NA2/NA2 PMNLs. To evaluate in vivo significance of Fc gamma RIIa and Fc gamma RIIIb allotypes, we analyzed Fc gamma R allotypes in children with bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Fc gamma RII and Fc gamma RIIIb polymorphisms were determined by using quantitative flow cytometry. Fc gamma RIIa were studied in 23 children with bacterial meningitis and 50 healthy Turkish controls, and Fc gamma IIIb in 18 and 43 such individuals, respectively. The distribution of Fc gamma RIIa in the healthy Turkish control group was found to be significantly different from that in the Chinese and Japanese population (p < 0.05), but similar to that of the white population in the USA and the Netherlands. No case (0%) had the Fc gamma RII-H/H-131 Fc gamma RIIIb-NA1/NA1 the corresponding figure in the controls was 4 (9.3%). Homozygous Fc gamma RIIa-H/H-131 phenotype was underrepresented with borderline significance (p: 0.057) in patients below two years of age in comparison with the healthy subjects and with patients with meningitis over two years of age (p: 0.059). Although the study needs to be conducted in a large series of patients in order to draw a firm conclusion, Fc gamma RIIa polymorphism may be a contributing factor to the increased susceptibility to meningitis with encapsulated bacteria in children below two years of age.     

Toll样受体4在原发性肾病综合征患儿肾组织及外周血中表达的意义

目的探讨Toll样受体4(TLR4)在原发性肾病综合征(INS)患儿肾组织及外周血中的表达及意义。方法采集2015年10月至2018年6月在新乡医学院第一附属医院确诊为INS的78例患儿肾活检组织及21例儿童正常肾组织(对照组1),应用免疫组织化学方法检测标本中TLR4表达水平,比较INS不同肾脏病理类型、不同临床分型中TLR4表达水平的差异,分析其与24 h尿蛋白、血清清蛋白的相关性;应用酶联免疫吸附试验(ELISA)检测INS患儿治疗前(活动期)及治疗后(缓解期)和23例健康儿童(对照组2)外周血中TLR4表达水平,比较INS不同肾脏病理类型、不同临床分型患儿血清中TLR4表达水平的差异,分析其与24 h尿蛋白、血清清蛋白的相关性;对INS患儿肾小管中TLR4的表达水平与血清TLR4的表达水平进行相关性分析。结果1.与正常肾组织TLR4水平[(0.93±0.26)%]比较,TLR4在各型INS患儿肾小球及肾间质的表达[系膜增生性肾小球肾炎(MsPNG)型:(0.93±0.21)%、局灶节段性肾小球硬化(FSGS)型:(1.02±0.25)%、膜性肾病(MN)型(1.03±0.09)%、微小病变(MCD)型(1.02±0.27)%]差异无统计学意义(F=0.741,P=0.562);而肾小管TLR4的表达水平明显增高[MCD型:(82.94±4.62)%、MN型:(63.54±1.98)%、MsPGN型:(42.32±2.97)%、FSGS型:(22.60±2.07)%],差异有统计学意义(F=1929.842,P<0.01),其中MCD型INS患儿肾小管TLR4表达水平较MN型、MsPGN型、FSGS型明显增高,差异均有统计学意义(均P<0.01);肾小管TLR4在临床分型为激素敏感型肾病综合征(SSNS型)肾脏组织中表达最高,在激素耐药型肾病综合征(SRNS)型表达最低,差异有统计学意义(F=220.951,P<0.01)。2.活动期INS患儿血清TLR4表达[MsPNG型:(143.36±12.99)ng/L、FSGS型(75.94±7.29)ng/L、MN型(210.22±14.66)ng/L、MCD型(283.93±21.58)ng/L]显著高于缓解期患儿[MsPNG型:(29.51±4.93)ng/L、FSGS型(15.66±3.78)ng/L、MN型(45.40±5.73)ng/L、MCD型(62.29±7.90)ng/L]及对照组2儿童[(0.69±0.33)ng/L],差异均有统计学意义(均P<0.01);且缓解期INS患儿血清TLR4的表达水平高于对照组2儿童,差异有统计学意义(F=286.287,P<0.01)。活动期及缓解期INS患儿血清TLR4的表达水平均以MCD型最高,其次为MN型,而FSGS型最低;血清TLR4在临床分型为SSNS型表达最高,SRNS型表达最低,差异有统计学意义(F=147.438,P<0.01)。3.INS患儿肾小管中TLR4的表达水平[(62.82±20.94)%]与其活动期血清中TLR4的表达水平[(213.26±73.33)ng/L]呈正相关(r=0.852,P<0.05);INS患儿肾小管及活动期血清TLR4的表达水平均与24 h尿蛋白水平[(123.05±33.55)mg/kg]均呈正相关(r=0.401、0.427,均P<0.05),与血清清蛋白水平[(19.54±3.55)g/L]均呈负相关(r=-0.602、-0.617,均P<0.05)。结论TLR4在INS患儿肾小管及血清中表达增高,且表达水平可能与不同肾脏病理类型及临床分型有关,与疾病活动具有相关性。     

Nasopharyngeal carriage of meningococcus and meningococcal meningitis in Sokoto, Nigeria

In an attempt to determine the epidemiology of meningococcal diseases in Sokoto, Nigeria, nasopharyngeal carriage of meningococcus was studied among the groups at the greatest risk of the disease, i.e. children and young adults. Of 726 subjects sampled, 45 (6.2%) carried meningococcus. Sixteen (35.6%) of the 45 isolates belonged to serogroup B. Others were as follows: group A, 8 (17.8%), C, 5 (11.1%), D, 1 (2.2%) and non-groupable 11 (24.4%). Clinical cases encountered during the period were caused by serogroups A (5, 62.5%) and C (3, 37.5%). A male:female carriage ratio of 1.2:1 was recorded for the potential epidemic serogroups, A and C (chi2 = 1.0091; p>0.05), while the clinical case ratio for the genders was 1.8:1 (chi = 16.1619; p<0.001). The 5-9-y-old age group carried meningococci more frequently (8.5%) than other age brackets, and also registered the highest incidence (46.5%) of the cases. Closeness of contact with a clinical case increased the carriage of the strain of the case (chi2 = 33.3940; p<0.001). Rural dwellers carried meningococcus more frequently than urban dwellers (chi2 = 9.5591; p<0.05). The season had no consistent influence on carriage rates, even though it significantly influenced the outbreaks of the disease. Mass vaccination with polysaccharide vaccine and improved living conditions appear to be the most practical ways to control meningococcal diseases in Africa.