Risk Factors For Meningococcal Disease Research Articles

Proceedings of the Expert Consensus Group meeting on meningococcal serogroup B disease burden and prevention in India

ABSTRACT Meningococcal disease is highly transmissible, life-threatening and leaves significant sequelae in survivors. Every year, India, which has a plethora of risk factors for meningococcal disease, reports around 3000 endemic cases. However, the overall disease burden and serogroup distribution are unknown, creating a setting of general disease negligence and unawareness. Vaccination with quadrivalent meningococcal conjugate vaccine A, C, W, and Y is only recommended for high-risk children, and there is no overall guidance for meningococcal serogroup B (MenB) vaccination. MenB vaccines, which recently have been licensed in many countries but not in India, have significantly aided the fight against meningococcal disease. However, these MenB vaccines are not available in India. An Expert Consensus Group meeting was held with leading meningococcal disease experts to better understand the current disease epidemiology, particularly serogroup B, the prevalence gaps, and feasible ways to bridge them. The proceedings are presented in this paper.

Risk factors for meningococcal disease in children and adolescents: a systematic review and META-analysis.

Invasive meningococcal disease (IMD) remains a major cause of mortality and morbidity in children worldwide. A systemic review in PubMed and Cochrane Controlled Trials Register was performed for articles on risk factors for IMD in children and adolescents published during a 20-year period (19/09/1998 to 19/09/2018). Inclusion and exclusion criteria were established and applied. The data were meta-analyzed using random-effect model and the results were presented on forest plots separately for each risk factor. We identified 12,559 studies (duplicates removed). Titles, abstracts, and full texts were screened and finally, six studies (five case-control and one cohort study) were included in qualitative synthesis, five in meta-analysis. The median age of meningococcal disease (MD) cases was 72.2months (0-19years). Household crowding, smoking exposure, close relationships, and recent respiratory tract infections conferred a more than twofold risk for IMD in exposed individuals compared to controls [overcrowded living OR 2.52 (95% CI 1.75-3.63), exposure to smoke OR 2.10 (95% CI 1.00-4.39), kissing OR 2.00 (95% CI: 1.13-3.51), and recent respiratory tract infection OR 3.13 (95% CI 2.02-4.86)]. Attendance of religious events was associated with a decreased risk [0.47 (95% CI, 0.28-0.79)].Conclusion: Our review highlights the importance of individual characteristics as risk factors for IMD in childhood and adolescence. Preventive policies may consider individual as well as social-environmental factors to target individuals at risk.What is Known:• Close relationships, household crowding, and recent respiratory tract infections are major risk factors for IMD.• Passive smoking is a major risk factor for IMD.What is New:• Intimate kissing, household crowding, and passive smoking were found to double the risk of IMD.• Recent respiratory tract infections almost tripled the risk for IMD.

Meningococcal Disease Surveillance in Men Who Have Sex with Men - United States, 2015-2016.

Meningococcal disease is a rare, but serious, bacterial infection that progresses rapidly and can be life-threatening, even with prompt antibiotic treatment. Men who have sex with men (MSM) have previously been reported to be at increased risk for meningococcal disease compared with other men, and recent outbreaks of serogroup C meningococcal disease among MSM have occurred (1). However, the epidemiology of meningococcal disease among MSM in the United States is not well described, in part, because information about MSM has not historically been collected as part of routine meningococcal disease surveillance. To better characterize and identify risk factors for meningococcal disease in general, supplementary data and isolates have been collected since 2015 through enhanced meningococcal disease surveillance activities. During 2015-2016, 271 cases of meningococcal disease in men aged ≥18 years were reported to the National Notifiable Diseases Surveillance System (NNDSS) in 45 states participating in this enhanced surveillance. Forty-eight (17.7%) cases were in men identified as MSM, including 17 (37.8%) with human immunodeficiency virus (HIV) infection. Among MSM, 39 (84.8%) cases were caused by Neisseria meningitidis serogroup C, whereas this serogroup was responsible for only 16.4% of cases among men who were not known to be MSM (non-MSM). Despite improvements in surveillance, MSM likely remain underascertained among men with meningococcal disease. Improved surveillance data are needed to understand the prevalence of and risk for meningococcal disease among MSM and inform policy and prevention strategies. Vaccination with quadrivalent meningococcal conjugate (MenACWY) vaccine is recommended for the control of meningococcal disease outbreaks caused by serogroups A, C, W, or Y, including during outbreaks among MSM; in addition, all persons aged ≥2 months with HIV infection should receive MenACWY vaccine because of the increased risk for meningococcal disease.

The threat of meningococcal disease during the Hajj and Umrah mass gatherings: A comprehensive review.

The Hajj and Umrah mass gatherings represent many of the risk factors for meningococcal disease and have historically been associated with both local and international outbreaks of the disease. The implementation of strict preventative measures including mandatory meningococcal vaccination with the quadrivalent (A,C,Y,W) vaccine has prevented pilgrimage-associated meningococcal outbreaks and significantly reduced the incidence of the disease at these events. However, meningococcal disease remains an important public health threat at the Hajj and Umrah due in part to the evolving nature of the disease, characterized with diverse and varying geographic trends, fluctuations in incidence and shifts in serogroups and genotypes. In addition, the current Hajj and Umrah meningococcal disease preventative measure do not protect against all invasive serogroups and do not necessarily affect carriage and transmission as the polysaccharide vaccine is still widely used. As a consequence, these events are still susceptible to outbreaks of the disease including those due to serogroups not included in the required vaccines such as serogroups B and X. In this context, despite the global decline in incidence of meningococcal disease, including that cause by serogroup B, the increased predominance of serogroup B disease in many countries, including countries with large Muslim populations, and the emergence of serogroup X in the African meningitis belt, are particularly concerning. Continued and strict surveillance of meningococcal diseases nationally and globally, especially in Muslim countries, is essential in detecting, understanding, and predicting the changes in the epidemiology of the disease and informing appropriate prevention and control strategies during these events. The current meningococcal disease preventative measures for Hajj and Umrah should continue to be strictly implemented, reviewed regularly and updated in accordance with changes in the epidemiology of meningococcal disease and availability of new preventative tools including new vaccines.

Case-Control Study of Risk Factors for Meningococcal Disease in Chile.

An outbreak of meningococcal disease with a case-fatality rate of 30% and caused by predominantly serogroup W of Neisseria meningitidis began in Chile in 2012. This outbreak required a case−control study to assess determinants and risk factors for infection. We identified confirmed cases during January 2012−March 2013 and selected controls by random sampling of the population, matched for age and sex, resulting in 135 case-patients and 618 controls. Sociodemographic variables, habits, and previous illnesses were studied. Analyses yielded adjusted odds ratios as estimators of the probability of disease development. Results indicated that conditions of social vulnerability, such as low income and overcrowding, as well as familial history of this disease and clinical histories, especially chronic diseases and hospitalization for respiratory conditions, increased the probability of illness. Findings should contribute to direction of intersectoral public policies toward a highly vulnerable social group to enable them to improve their living conditions and health.

A Case-Control Study on the Risk Factors for Meningococcal Disease among Children in Greece.

PurposeThe aim of this study was to identify environmental or genetic risk factors that are associated with invasive meningococcal disease (IMD) in children in Greece.MethodsA case-control study was performed in 133 children (44 cases and 89 controls) aged between 0–14 years, who were hospitalized in a children's hospital in Athens. Demographics and possible risk factors were collected by the use of a structured questionnaire. To investigate the association of mannose binding lectin (MBL) with IMD, a frequency analysis of the haplotypes of the MBL2 gene and quantitative measurement of MBL serum protein levels were performed using Nanogen NanoChipR 400 technology and immuno-enzyme techniques, respectively.ResultsThe multivariate analysis revealed that changes in a child's life setting (relocation or vacation, OR = 7.16), paternal smoking (OR = 4.51), upper respiratory tract infection within the previous month (OR = 3.04) and the density of people in the house/100m2 (OR = 3.16), were independent risk factors associated with IMD. Overall 18.8% of patients had a MBL2 genotype with low functionality compared to 10.1% of healthy controls, but this was not statistically significant (p = 0.189).ConclusionPrevention strategies aimed at reducing parental smoking and other risk factors identified in this study could decrease the risk of IMD among children in Greece.

N. meningitidis and TLR Polymorphisms: A Fascinating Immunomodulatory Network.

N. meningitidis infections represent a global health problem that can lead to the development of serious permanent sequelae. Although the use of antibiotics and prevention via vaccination have reduced the incidence of meningococcal disease, our understanding regarding N. meningitidis pathogenesis is still limited, especially of those mechanisms responsible for IMD and fulminant or deadly septic shock. These severe clinical presentations occur in a limited number of subjects, whereas about 10% of healthy individuals are estimated to carry the bacteria as a commensal. Since TLR activation is involved in the defense against N. meningitidis, several studies have highlighted the association between host TLR SNPs and a higher susceptibility and severity of N. meningitidis infections. Moreover, TLR SNPs induced variations in immunological responses and in their persistence upon vaccination against meningococcal disease. In the absence of mass vaccination programs, the early identification of risk factors for meningococcal disease would be recommended in order to start immunization strategies and antibiotic treatment in those subjects carrying the risk variants. In addition, it could allow us to identify individuals with a higher risk for severe disease and sequelae in order to develop a personalized healthcare of high-risk subjects based on their genomic profile. In this review, we have illustrated important preliminary correlations between TLR variants and meningococcal susceptibility/severity and with vaccine-induced immune responses.

Invasive Meningococcal Disease in Men Who Have Sex With Men

Invasive Meningococcal Disease in Men Who Have Sex With Men

Risk Factors for Meningococcal Disease in Students in Grades 9–12

Meningococcal disease is a serious problem in adolescents, including high school students. Universal immunization of adolescents with meningococcal conjugate vaccine was recently recommended. We studied risk factors for meningococcal disease in students in grades 9-12. This was a matched case-control study using surveillance for meningococcal disease in students in grades 9-12 in sites throughout the United States. For each case-patient, up to 4 controls were selected from the home room classroom. All subjects answered an extensive questionnaire. Logistic regression was performed to identify risk factors associated with meningococcal disease. Meningococcal isolates were characterized. Of 69 eligible patients, 49 (71%) were enrolled and had at least 1 control. Isolates were available for 59 (86%) cases. Attending at least 1 barbeque or picnic [matched odds ratio (MOR): 0.26, P value = 0.003] or school dance (MOR: 0.30, P = 0.04) were independently associated with decreased risk of meningococcal disease. Male gender (MOR: 2.94, P = 0.009), upper respiratory infection symptoms (MOR: 2.43, P = 0.04), marijuana use (MOR: 4.21, P = 0.009), and nightclub/disco attendance (MOR: 3.30, P = 0.04) were associated with increased risk. Among 54 students not from Oregon (where serogroup B strains predominate) with available serogroup, 38 (73.1%) cases were potentially vaccine preventable: 18 (34.6%) serogroup C, 19 (36.5%) serogroup Y, and 1 (1.9%) serogroup W-135. Certain behaviors increase the risk of meningococcal infection, whereas others are associated with decreased risk. Most meningococcal disease in high school students can be prevented if recommendations on use of meningococcal conjugate vaccine are implemented.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

. Tully J., Viner R.M., Coen P.G., Stuart J.M., Zambon M., Peckham C., Booth C., Klein N., Kaczmarski E. & Booy R. ( 2006 ) , 332 , 445 – 450 . Objective To examine biological and social risk factors for meningococcal disease in adolescents.Design Prospective, population‐based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner.Setting Six contiguous regions of England, which represent some 65% of the country’s population.Participants Fifteen‐to‐nineteen‐year‐olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls.Methods Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression.Results A total of 144 case–control pairs were recruited [74 male (51%); median age 17.6 years]. In total, 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4–5.9), intimate kissing with multiple partners (3.7, 1.7–8.1), being a university student (3.4, 1.2–10) and preterm birth (3.7, 1.0–13.5). Religious observance (0.09, 0.02–0.6) and meningococcal vaccination (0.12, 0.04–0.4) were associated with protection.Conclusions Activities and events increasing risk for meningococcal disease in adolescence are different from those in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

Objective To examine biological and social risk factors for meningococcal disease in adolescents.Design Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls...

Social and Environmental Influences Affecting the Risk of Development of Meningococcal Disease: Considerations for Prehospital Care

After briefly reviewing the clinical features, major sequelae and initial treatment of invasive meningococcal disease, and reviewing the international and domestic incidence of meningococcal disease, the epidemiological risk factors for meningococcal disease found in the literature are summarised. These findings and the heterogeneity of sub-population risk, especially in relation to indigenous populations, are then discussed. The implications of these discussions are then applied to paramedic practice as a component of primary health care. The author argues that consideration of such data is important in developing recommendations for the development of system planning and clinical practice guidelines.

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.

Increased Attack Rate of Meningococcal Disease in Children With a Pregnant Mother

To investigate the relationship between meningococcal disease and family composition, especially pregnancy in mothers. This was a retrospective matched case-control study. Case patients were children (aged 0-18 years) who had meningococcal disease and were admitted to our hospital from 1990 to 2002. Children who were admitted to 1 of the general pediatric wards of the hospital during the same period and did not have meningococcal disease served as control subjects. One control subject (matched according to gender, age, and year, and season of admission) was enrolled for each case patient. Parents of case patients and control subjects were asked to fill out a questionnaire on family composition, birth dates of siblings, and pregnancy at the time of hospital admission. A total of 88 matched case-control pairs were included. In the case group, 17 (19%) mothers reported having been pregnant at the time of hospitalization of their child, compared with 2 (2%) in the control group. Other family characteristics were not different. After adjustment for confounding factors, pregnancy of mothers remained a significant risk factor for meningococcal disease in children (odds ratio: 11.7; 95% confidence interval: 2.6-53.9). Meningococcal disease in children was highly associated with pregnancy of the patient's mother during hospitalization. Mechanisms by which the presence of a pregnant mother in a family affects the attack rate of meningococcal disease in her children need additional investigation.

Including a time-of-year effect in the analysis of a matched case-control study.

Motivated by a matched case-control study to investigate potential risk factors for meningococcal disease amongst adolescents, we consider the analysis of matched case-control studies where disease incidence, and possibly other risk factors, vary with time of year. For the cases, the time of infection may be recorded. For controls, however, the recorded time is simply the time of data collection, which is shortly after the time of infection for the matched case, and so depends on the latter. We show that the effect of risk factors and interactions may be adjusted for the time of year effect in a standard conditional logistic regression analysis without introducing any bias. We also show that, if the time delay between data collection for cases and controls is constant, provided this delay is not very short, estimates of the time of year effect are approximately unbiased. In the case that the length of the delay varies over time, the estimate of the time of year effect is biased. We obtain an approximate expression for the degree of bias in this case.

Geographic correlation between deprivation and risk of meningococcal disease: an ecological study.

BackgroundMeningitis caused by Neisseria meningitidis is a serious infection which is most common in young children and adolescents. This study investigated the relationships between the incidence and age distribution of meningococcal disease, and socioeconomic environment.MethodsAn ecological design was used, including mapping using a Geographical Information System (GIS) at census ward level.ResultsIncidence of meningococcal disease was highest in the most deprived wards, with a relative risk of 1.97 (1.55 – 2.51). Mapping revealed geographical coincidence of deprivation and meningococcal disease, particularly in urban areas. Two-thirds of the increased incidence was due to cases in the under fives.ConclusionsThe results suggest that area deprivation is a risk factor for meningococcal disease, and that its effects are seen most in young children.

Heterozygous C8beta complement deficiency does not predispose to meningococcal disease.

We have identified 42 Russian patients with homozygous C8beta complement component deficiency, all of whom had experienced at least one episode of systemic meningococcal disease. About 90% of these individuals have a C --> T exchange in exon 9, leading to a premature stop codon. If, like the homozygous-deficient state, heterozygous C8beta deficiency constitutes a risk factor for meningococcal disease, it would be expected to be detected with increased frequency among individuals suffering from this disease. Using allele-specific polymerase chain reaction (PCR), we studied 153 consecutive patients with meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to determine the frequency of C8 null allele. No individuals with heterozygous C --> T exchange were identified among these 153 patients, despite the fact that seven persons were detected who had homozygous C8beta deficiency, caused by the same C --> T exchange in exon 9, and one patient who had C7 component deficiency. Thus, heterozygous deficiency, although more frequent than homozygous deficiency in the general population, does not result in a substantial increase in susceptibility to meningococcal disease.

Severe meningococcal disease in childhood

Severe meningococcal disease in childhood

Stress, risk-behaviours and meningococcal disease in teenagers

Purpose: Meningococcal disease (MD) is a life-threatening condition with a bimodal age distribution. The teenage peak in incidence is poorly understood. Developmental and behavioural factors associated with adolescence may be important risk factors. We tested the hypotheses that life stress, intimate relationships, smoking, alcohol and substance use are risk factors for MD in adolescents.

Day-care and meningococcal disease in young children.

The Republic of Ireland has the highest incidence of meningococcal disease in Europe with 40% of all cases occurring in children under the age of 5 years. Attending day-care increases the risk of certain infections, including Haemophilus influenzae type b (Hib) meningitis. The risk of meningococcal disease associated with day-care is not known. We conducted a case-control study among pre-school children with 130 laboratory-confirmed cases and 390 controls, matched on age, gender and place of residence, to determine if day-care attendance was a risk factor for meningococcal disease. Multivariate analysis showed that day-care attenders had a lower risk of disease than non-attenders (OR 0.3, 95% CI 0.1-0.7) whereas the number of adults in a household, and household crowding were independent risk factors for disease. Asymptomatic carriers of Neisseria meningitidis are the main source of transmission and these carriers are usually adults. Regular day-care attendance may reduce this risk by removing children from close and prolonged contact with adults.