Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.     

Meningococcal disease in urban south western Sydney, 1990–1994

Background: There has been a sustained increase in incidence of meningococcal disease throughout Australia since 1987. In south western Sydney the incidence is higher than the national rate and a cluster of cases occurred in 1991 resulting in a widespread vaccination programme. Aims: To investigate the clinical demographics of patients with meningococcal disease treated in south western Sydney, and to differentiate meningococcal strains to understand better the epidemiology in this urban setting. In addition, to investigate whether delays in diagnosis of meningococcal disease and institution of appropriate treatment were occurring. Methods: Retrospective classification of notified cases as meningitis, septicaemia, meningitis/septicaemia, and other syndromes. Clinical information recorded to establish patterns of disease, delays in diagnosis and appropriate treatment, and outcome. Microbiological classification of organisms isolated by serogroup, serotype and subtype. Results: Meningococcal disease primarily affects young children in winter months in south western Sydney, with a secondary peak of incidence in the 15–20 year old age group. 20.7% presented with meningitis only, 22.4% with septicaemia only, and 53.4% with meningitis/septicaemia. There was a delay in diagnosis and institution of appropriate treatment of more than two hours in 21/58 (36.2%) patients including three of the six who died. No patient had received a parenteral antibiotic prior to coming to hospital - 18.9% had received an oral antibiotic. The use of antibiotics before diagnostic lumbar puncture decreased the number of positive CSF cultures. However, in all but one patient with negative cultures there was other microbiological evidence of meningococcal disease. The mortality rate was highest (30.8%) in patients with septicaemia only, 6.5% in patients with meningitis/septicaemia and 0% in patients with meningitis only. Serogroup C was the predominant organism in all age groups. The predominant serotype was 2b (80% of serogroup C isolates). Subtypes were more variable but P1.2 occurred in 66.7% of serogroup C strains. Conclusions: There is a need for more education in our Health Area to improve the time taken to diagnose and institute appropriate treatment. The predominance of serogroup C is unusual in urban Australia where national data show serogroup B organisms predominate. Meningococci of phenotype C:2b:Pl.2 have continued to cause disease in our Health Area for the past five years. This phenotype is uncommon in other areas of Australia.     

Emergence of endemic serogroup W135 meningococcal disease associated with a high mortality rate in South Africa.

BACKGROUND: In the African meningitis belt, Neisseria meningitidis serogroup W135 has emerged as a cause of epidemic disease. The establishment of W135 as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000-2005. The system was enhanced in 2003 to include clinical data collection of cases from sentinel sites. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 2135 cases of invasive meningococcal disease were reported, of which 1113 (52%) occurred in Gauteng Province, South Africa. In this province, rates of disease increased from 0.8 cases per 100,000 persons in 2000 to 4.0 cases per 100,000 persons in 2005; the percentage due to serogroup W135 increased from 7% (4 of 54 cases) to 75% (221 of 295 cases). The median age of patients infected with serogroup W135 was 5 years (interquartile range, 2-23 years), compared with 21 years (range, 8-26 years) for those infected with serogroup A (P<.001). The incidence of W135 disease increased in all age groups. Rates were highest among infants (age, <1 year), increasing from 5.1 cases per 100,000 persons in 2003 to 21.5 cases per 100,000 persons in 2005. Overall case-fatality rates doubled, from 11% in 2003 to 22% in 2005. Serogroup W135 was more likely to cause meningococcemia than was serogroup A (82 [28%] of 297 cases vs. 11 [8%] of 141 cases; odds ratio, 8.9, 95% confidence interval, 2.2-36.3). A total of 285 (95%) of 301 serogroup W135 isolates were identified as 1 clone by pulsed-field gel electrophoresis; 7 representative strains belonged to the ST-11/ET-37 complex. CONCLUSIONS: Serogroup W135 has become endemic in Gauteng, South Africa, causing disease of greater severity than did the previous predominant serogroup A strain.     

Meningococcal disease in Italy

In 1985, nationwide surveillance of meningococcal disease aimed at establishing appropriate guidelines for prophylaxis started in Italy. The incidence of disease was 1.1/100,000 in 1985 and 0.6/100,000 in 1987. This decreasing trend was particularly evident among military recruits (from 17.3/100,000 in 1985 to 5/100,000 in 1987), reflecting the use of bivalent serogroup (A + C) meningococcal polysaccharide vaccine in all new recruits since January 1987. The age distribution of cases was statistically different from that observed during the 1970s (P less than 0.001), with a shift towards older age groups. Men have been in the majority (516 vs. 358, P less than 0.0000001). Group C has been the most common serogroup encountered (72.2%), while only 18% of the isolates belonged to serogroup B. Among military recruits, serogroup C accounted for 92% (81/88) of the cases. The proportion of strains resistant to sulphonamides was 67%, while only 3% strains were resistant to rifampicin and to minocycline. Reduced susceptibility to ampicillin and to penicillin was observed in 3 and 4% strains respectively. Nine secondary cases were all due to failure in the administration of chemoprophylaxis (sulphonamide given in seven cases, prophylaxis not attempted in two cases). Immunisation of all new military recruits and effective chemoprophylaxis of close contacts of cases are the major guidelines provided by the National Meningitis Surveillance Programme.     

Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000

In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.     

Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine

The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.     

Epidemiology of meningococcal disease in Denmark 1980-1988.

Based on epidemiological data of notified cases of meningococcal disease (MD) in Denmark during the period 1980-88 the recommendations for prophylaxis are evaluated. In 1986 the incidence of MD increased about 60% to 5.5 per 100,000 population. The clinical diagnosis of MD was verified by culture of Neisseria meningitidis in 79% of notified cases. About 40% of all patients were less than 4 years of age. The mortality in 1988 was found to be 10%. Serogroup B disease accounted for about 80% of the cases. Two co-primary and 28 secondary cases were registered. Two major outbreaks of serogroup C disease occurred in 1984 and 1986, respectively. In small clusters of 2-3 cases within socially well-defined groups the recommendations for prophylaxis are sufficient. But for the new pattern of clusters spread over months to years in certain geographical areas or open social groups, especially among teenagers, the existing recommendations are insufficient. The occurrence of localized clusters of serogroup B disease emphasises the need for a vaccine against serogroup B disease.     

Invasive haemophilus influenzae and meningococcal infections in Finland. A climatic, epidemiologic and clinical approach

A nationwide epidemiological survey on invasive (blood and/or CSF culture positive) Haemophilus influenzae (HI) and meningococcal infections was performed in Finland in 1976-1980. The mean annual incidence of HI infection was 3.4/100,000 inhabitants (813 cases) vs. 2.0/100,000 (469 cases) of meningococcal infection. HI infections showed no geographical predilection, but meningococcal disease, mainly of group B, was more common in northern than in southern Finland (p less than 0.005). Meningitis accounted for 61% of the HI and 91% of the meningococcal infections. The overall fatality rates were 3.1% and 7.9%, respectively. Children accounted for 94% of the HI and 59% of the meningococcal cases. The overall annual incidence of bacterial meningitis in children (less than 15 years) was 19/100,000; in children less than 5 years it was 52/100,000. HI was the most common (62%) causative agent, followed by meningococci (18%) and pneumococci (5%). The fatality rate was 4%. Major neurological sequelae were found in 5%, minor ones in 16%. It was calculated that 42% of the cases of meningitis could have been prevented by vaccines now available on the market. Vaccines now under field investigation may increase the preventability to about 65%.     

Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010

ABSTRACT: BACKGROUND: Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada. METHODS: We retrieved information on confirmed IMD cases reported to Ontario's reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate (NNV) using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70 % and 80 %, and assuming only direct protection (no herd effects). RESULTS: A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4 % occurred in infants, of which 72.7 % were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7 % overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease. CONCLUSIONS: Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.     

Central nervous system infections in Benghazi, Libya: experience from a community-based adult medical neurology set-up

During a 2-year period, a total of 43 incident cases of central nervous system infections occurred in the adult (aged 15 years and above) population in Benghazi, Libya. This comprised 17 patients with aseptic meningitis, 10 acute bacterial meningitis, four tuberculous meningitis, five encephalitis, four neurosyphilis, two hydatidosis and one bilharzial myelopathy. The aetiology of the aseptic meningitis and encephalitis could not be established. The annual incidence rates of aseptic, septic and tuberculous meningitis, and encephalitis were 3.4, 2, 0.8 and 1 per 100,000 population, respectively.     

Management of acute meningococcal septicaemia in Al-Nasser Paediatric Hospital: a retrospective cohort study

Background

Acute meningococcal septicaemia is a fulminant disease, and mortality and long-term morbidity can be very high if not treated appropriately. We aimed to evaluate case fatality rate of all children admitted with acute meningococcal septicaemia.

Outbreak of infection caused by Neisseria meningitidis group C type 2 in a nursery

An outbreak of meningococcal infection which took place in a nursery in Rioja, Spain, is reported. Between November 1981 and February 1982, 11 patients had meningitis with or without septicaemia. Two died. Three meningococcal strains from the patients isolated were studied. All three were group C type 2 and were resistant to sulphadiazine (MIC 50 mg/l) but susceptible to penicillin, ampicillin, chloramphenicol, rifampicin and spiramycin. This outbreak took place during an epidemic in which serogroup B was the most prevalent in Spain. Two surveys before and after chemoprophylaxis were made to determine the carrier rate in the nursery population. The strain causing the outbreak was found in 2.5 and 4 per cent of persons respectively. Rifampicin was administered to all carriers after the first survey and to carriers of the virulent strain after the second survey. The remaining children were given polysaccharide C vaccine. No more cases arose after this last prophylactic measure.     

Surveillance of invasive meningococcal disease in the Czech Republic

Routine notification of invasive meningococcal disease has a long tradition in the Czech Republic: mortality data are available from 1921 and morbidity data from 1943. The collection of Neisseria meningitidis strains kept in the NRL for Meningococcal Infections in Prague dates from 1970 onwards, and represents more than 3500 strains isolated from invasive disease and their contacts, from healthy carriers and from respiratory infection. Analysis of these strains showed that the Czech meningococcal population is different from that seen in western Europe. In 1993, the incidence serogroup C meningococcal disease increased and was associated with the emergence of the hypervirulent complex Neisseria meningitidis C, ST-11, ET-15/37, and caused an increase in the incidence of invasive meningococcal disease which peaked in 1995 (2.2/100,000). A vaccination strategy targeting the part of the population at highest risk of invasive meningococcal disease was adopted in the country.     

Carriage of Neisseria meningitidis in a semi-isolated arctic community.

The carriage of Neisseria meningitidis was examined in the Norwegian population of Svalbard (1150 persons) after a fatal case of meningococcal septicaemia. The overall carrier rate was 39.0%. The rate was highest among males (47.8%), with a maximum of 63.4% in the age group 15-24 years. The carrier rate was low among children aged 3 to 15 years (6.5%). Children below 3 years were frequent meningococcal carriers, however (37.5%). Sulphonamide-resistant strains were often found, 22.6% of the total material being resistant. Group B was the most frequent serogroup, and accounted for 44.5% of the isolated strains. Non-groupable strains were second in frequency (23.8%), followed by group Y (15.8%). Only a few strains belonged to the serogroups A, C, X and Z. N. lactamica was isolated from 26.9% of children below 15 years, but seldom in older age groups.     

Meningococcal disease in a large urban population (Barcelona, 1987-1992): predictors of dismal prognosis. Barcelona Meningococcal Disease Surveillance Group.

CONTEXT: Studies on meningococcal disease in large urban communities have rarely been performed and are usually based on passive epidemiologic surveillance. Active surveillance may provide new insights. OBJECTIVES: To determine epidemiologic, clinical, and bacteriological characteristics and predictors of dismal prognosis (death and sequelae) in meningococcal disease. DESIGN: Prospective, population-based study. SETTING: All the acute care hospitals (n = 24) in Barcelona, Spain. PATIENT: The 643 patients whose conditions were diagnosed from 1987 through 1992 were detected by 2 active surveillance methods. OUTCOME MEASURES: Incidence and notification to Public Health Service. Clinical and bacteriological features were determined. Dismal prognosis predictors were determined by logistic regression. RESULTS: Average annual incidence was 6.41 per 100,000 inhabitants, with no clear trend of change (P = .08). Sensitivity of the Public Health Service surveillance system was 69.1%. Children younger than 10 years from the inner city were at higher risk than those from the highest income district (relative risk, 3.00; 95% confidence interval [CI], 1.84-5.06). Increasing annual incidence of serogroup C (0.82-1.29/100,000; P = .008) and decreasing incidence of serogroup B (5.11-2.82/100,000; P = .004) was noted. Average annual mortality was 0.40 per 100,000 inhabitants, while the annual average potential years of life lost was 18 per 100,000 inhabitants. Overall case-fatality rate was 6.4%. Independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 63; 95% CI, 21-194), focal neurologic signs (OR, 10; 95% CI, 3-30), and age 60 years or older (OR, 6; 95% CI, 2-17), whereas preadmission antibiotic therapy was associated with favorable outcome (OR, 0.07; 95% CI, 0.02-0.3). Four percent of survivors presented with sequelae. Independent predictors of sequelae were hemorrhagic diathesis (OR, 21; 95% CI, 3-131), focal neurologic signs (OR, 16; 95% CI, 5-53), age 60 years or older (OR, 7; 95% CI, 2-26), and age between 15 and 59 years (OR, 5; 95% CI, 2-14), whereas preadmission antibiotic therapy had a protective effect (OR, 0.2; 95% CI, 0.04-0.5). CONCLUSIONS: Active epidemiologic surveillance significantly improved detection of cases and allowed us to observe that meningococcal disease still causes much morbidity and mortality, especially among children living in the inner city. Hemorrhagic diathesis, focal neurologic signs, and age were independent predictors of dismal prognosis, whereas preadmission antibiotic therapy had a protective effect.     

Molecular characteristics of Neisseria meningitidis strains isolated in Burkina Faso in 2001

In the course of an epidemic of meningitis in Burkina Faso in 2001, 27 cerebrospinal fluid samples from patients in 7 districts were forwarded to Norway for isolation and characterization of the causative agents. Neisseria meningitidis was isolated from 13 (48%) samples. The isolates were analysed using serological and genetic methods. Of the 13 strains, 4 were serogroup A, serotype 21:P1.9, sequence type (ST)-5 and belonged to clonal subgroup III, while the remaining 9 strains were serogroup W135, serotype 2a:P1.5,2, ST-11 and belonged to the electrophoretic type-37 complex. PCR analyses revealed meningococcal DNA in 13/14 culture-negative samples. Sequence analysis of the PCR products demonstrated that at least 3 different meningococcal strains were responsible for these 13 cases. Our results show that the W135 strain associated with the 2000 hajj (Muslim pilgrimage) outbreak was a significant cause of disease in Burkina Faso in 2001. Further studies are warranted to determine whether W135 is about to replace serogroup A in sub-Saharan Africa.     

Features of a large epidemic of group A meningococcal meningitis in Khartoum, Sudan in 1988

A large epidemic (February-August 1988) of group A sulphonamide resistant, clone III-1 meningococcal meningitis in Khartoum, Sudan is described. A total of 10,099 cases were admitted to treatment centers with 8,397 cases during March and April, corresponding to an annual incidence of 1,679/100,000 inhabitants during this period. The age profile showed a high morbidity in adults (31% of the cases greater than or equal to 20 years). The male dominance was marked especially in the adult cases with a proportion of 3.2:1. The epidemic started during the hot and dry season and declined when the clouds came, humidity rose, temperature fell and a mass vaccination campaign had been implemented together with other epidemic precautions. Vaccination with a combined group A/C polysaccharide vaccine had been given 4 weeks-1 year before hospitalization to 11% of the children, 80% of whom were greater than 18 months of age. The estimated case fatality rate was 6.3%. Since 47% of the cases came from periurban and rural areas, the actual mortality during the epidemic might have been higher when considering those who may have died before reaching any of the treatment centres. Fatal cases had a short history of acute illness and a septic condition. Septicaemia was rare and seen in only 3.7% of the cases, the rest had acute purulent meningitis. Hearing loss/impairment and hemiplegia was diagnosed in 2-3% of the cases. The epidemiology, based on detailed typing/subtyping and restriction enzyme patterns of meningococcal strains, was apparently associated with the Mecca outbreak in August 1987.     

Secondary immunologically-caused myocarditis, pericarditis and exudative pleuritis due to meningococcal meningitis

Myocarditis, pericarditis and pleural effusion as secondary immunological reactions due to meningococcal meningitis are rare. Meningococcal meningitis is itself uncommon, with a morbidity of approximately 1.25 cases per 100,000 inhabitants per year in Germany. Cardial participation could be observed either primary infectious-toxic in the first week or secondary immunologic in the second week after disease onset. In our patient, six days after the onset of meningococcal meningitis (serogroup B) a distinct swelling of the myocardium appeared together with pericardial effusion in the absence of Waterhouse-Friderichsen syndrome. This case is proving difficult to tackle therapeutically due to repeated relapses.