Study On The Epidemiological Characteristics Of Meningococcal Disease In Anhui Province

BackgroundMeningococcal disease is a contagious disease caused by the bacterium N.meningitidis. It is still an important public heath issue because of theunexpected onset and rapid progress of the disease combined with a highcase-fatality rate (CFR). Meningococcal disease is mandatory notifiablein China. Among the 13 meningococcal serogroups defined by serologicreactivity of the meningococcal capsular polysaccharide, serogroups A, B,and C are the most commonly associated with the disease. In China, theleading causative agent of epidemics was serogroups A, and serogroup Acapsular polysaccharide vaccines have been used in infants and school-agedchildren since the beginning of the 1980s. Since then, the intervals betweenepidemics have become more irregular, and the number of cases ofmeningococcal meningitis has declined to a few per year. However, in recentyears, the number of meningococcal meningitis cases attributed to serogroupC has increased substantially in China. Anhui Province—a region situatedin middle China—is one of the areas where the first outbreak ofmeningococcal disease caused by serogroup C was found in China. Since thespring in 2003, the incidence of meningococcal disease due to serogroupC increased rapidly. Significant changes might have occurred inepidemiology features accompanying this incidence shift. There was few published report about the epidemiological characteristics of meningococcal disease caused by serogroup C in China. In order to propose appropriate preventive and control measures, the present study first focused on the epidemiological characteristics of meningococcal diseases caused by serogroup C in China. We evaluated epidemiological trends of meningococcal disease in Anhui province and examined demographic and clinical characteristics of the meningococcal cases caused by serogroup C in Hefei area to assess the impact of the disease.ObjectivesTo determine the shift of the epidemiologic characteristics of meningococcal disease in Anhui province and to provide valuable information for developing timely and appropriate public health interventions.MethodsData about the patients with meningococcal disease were collected according to the National Disease Surveillance System.The territories of Anhui province was divided by the Huaihe river and the Yangzi river into three areas: the middle part, southern part and northern area.During July. 2003 and June. 2007, information about the patients with meningococcal disease in Hefei city would collected with a uniform questionnaire including demographic characteristics, clinical presentations, and medications, etc. A total of 6 age groups, and the first 4 age groups in which coincide with the main levels of education in China, were selected. The statistical period was defined to follow the possible seasonal pattern, from July 1 to the next June 30. (e.g., 1 July 2003 to 30 June 2004 was regarded as the year, 2003–2004).The incidence rate and case fatality rate (CFR) were calculated according to year, age groups, and different areas. The proportion of the cases was calculated by age groups. Categorical variables were compared using chi-squared or a two-tailed Fisher's exact test. Median age of cases and death rates were calculated according to sex and the seasonality by monthly average incidence. Because data of age were not normally distributed, the difference of age between the sexes, death cases and survival cases was tested by nonparametric Mann-Whitney U Test. The association between clinical signs, symptoms, laboratory findings, sex, age and mortality was first examined by univariate logistic analysis. And then, these factors associated with death significantly would be further test by multivariate logistic analysis. The level of significance was fixed atα=0.05.ResultsFrom 1951 to 2007, a total of 799,387 cases with meningococcal disease was reported in Anhui province, the annual incidence rate was 28.90 per 100,000 population, 41,337 death cases, the mortality rate was 1.49 per 100,000 population and the average CFR was 5.17%. Three epidemic outbreaks of meningococcal meningitis occurred in the period, and the largest one was occurred during 1975 to 1979 with the peak incidence in 1977(729.35/100,000). In the pre-vaccine era, periodic epidemics occurred every 7–10 years. Serogroup A capsular polysaccharide vaccines have been used in infants and school-aged children since the beginning of the 1980s. Since then, these (serogroup A) epidemic cycles have become more irregular, the number of cases of meningococcal meningitis has declined to a few per year. But the incidence increased slightly every 10 years. Since spring in 2003, there were outbreaks of meningococcal disease caused by serogroup C in some local areas, the incidence of meningococcal disease in Anhui province increased. Meningococcal disease cases increased in winter (starting in October or December) with the incidence peak in April to May. The male-to-female ratio was 1.46:1, but the ratio was 0.70:1 in the patients age older than 25 years. When epidemics occurred throughout Anhui province, it often observed that the incidence increased early in the northern part than the other two areas, but in 2002, the outbreak caused by serogroup C was first found in the southern part of Anhui province.During the study period, the average incidence of meningococcal disease was 30.82/100,000,25.15/100,000 and 29.88/100,000 in the middle, southern and northern parts of Anhui province respectively, and the CFR was 4.37%,4.92% and 6.00% respectively.From July 2003 to June 2007, meningococcal disease was confirmed in 386 cases among the total population in Hefei area, the average annual incidence rate was 2.09 per 100,000 population. The N. meningitidis serogroup was identified in 135 cases (34.97%) of the Meningococcal disease cases—all in serogroup C. The median age of these patients was 15 years (age ranged from 2 months to 78 years). By age group, the highest incidence rate (6.6 per 100,000 population) and the highest proportion (31.35%) of cases occurring in aged 12–17 years old. 219 cases were male(56.74%) . Patients 6–21 years old were more likely to be male, with a male-to-female ratio of 1.6:1; the male-to-female ratio of the age group older than 21 years was 1:1.8. The average CFR was 7.3% with a peak of 16.90%—in children younger than 6 years old. Since winter 2003, a vaccination campaign was recommended and partially implemented, but the effectiveness of the vaccine was limited. 334(86.53%) with a sudden onset. 371 cases present fever (96.10%), 322 (88.42%) had vomiting, 311 (80.57%) was present nausea, 285 (73.83 percent) had stiff neck .and 278(72.02%) had headach. A total 28 fatal cases were reported, the average case fatality rate was 7.25%, the median age of death cases was 10 years (range from 2 months to 27 years), which was significantly younger than the living cases (15 years, range from 6 months to 78 years; Z=2.54, P=0.011). By univariate logistic analysis, the following factors were associated with death: headache, nausea, altered mental status, purpura or petechia, number of petechia>3, stiff neck, Neutrophil>80%, positive Kerning's sign, positive Brudzinski's signs and age younger than 12 years old (p < 0.05). Using a multivariate regression analysis model, number of petechia>3, Neutrophil>80%, and positive Brudzinski's signs were associated with increased risk of mortality. 21 clusters were identified. All the cluster cases were caused by serogroup C. The highest proportion of cases (19 cases, 35.19%) occurred in age group of 12 to 17 years. The carrier rate of Neisseria meningitides in heathy people is higher in midldle period (5.99%) than it in the early period (3.05%), and an increase in the carrier rate with the growth trends was observed.ConclusionsMeningococcal disease is always a public health problem in Anhui province. In the past, serogroups A was predominant in Anhui province. Since serogroup A capsular polysaccharide vaccines have been used in infants and school-aged children in the early 1980s, a significant decrease in incidence was observed. In the post-vaccine era, epidemic cycles have become more irregular, however, the incidence slightly increased approximately every 10 years was also observed. Recently, serogroup C replaced serogroup A as the most predominant serogroup and the incidence of meningococcal disease substantially increased in our area, changes in the age distribution of the cases that from younger to older-age categories was also observed. These phenomenons would be temporal in epidemics, further investigation and strengthening the capacities for epidemiologic and microbiologic surveillance of meningococcal disease is still necessary. Changs in the capsular polysaccharide of meningococci might be due to the additional effect of vaccine. To achieve full control of meningococcal disease, particularly since the epidemiology of disease is unpredictable and is continuously evolving, better the prevention measure and immunity policy is desirable. Men were more susceptible than women of the same age group. After the onset of the outbreak caused by serogroup C in Hefei area, a campaign to vaccinate people under 15 years of age with the meningococcal bivalent polysaccharide A/C vaccine was carried out, but our study showed that the effectiveness of the vaccine was limited. The incidence of October and/or November might be an alert sign for incidence in next year. The CFR of the patients caused by serogroup C is higher than it by serogroup A. Some clinical and laboratory features, such as number of petechia>3, Neutrophil>80%, and positive Brudzinski's signs were associated with fatal outcome.