Response thresholds for epidemic meningitis in sub-Saharan Africa following the introduction of MenAfriVac®

BackgroundSince 2010, countries in the African meningitis belt have been introducing a new serogroup A meningococcal conjugate vaccine (MenAfriVac^®) through mass campaigns. With the subsequent decline in meningitis due to Neisseria meningitidis serogroup A (NmA) and relative increase in meningitis due to other serogroups, mainly N. meningitidis serogroup W (NmW), the World Health Organisation (WHO) initiated a review of the incidence thresholds that guide response to meningitis epidemics in the African meningitis belt.MethodsMeningitis surveillance data from African meningitis belt countries from 2002 to 2013 were used to construct a single NmW dataset. The performance of different weekly attack rates, used as thresholds to initiate vaccination response, on preventing further cases was estimated. The cumulative seasonal attack rate used to define an epidemic was also varied.ResultsConsiderable variation in effect at different thresholds was observed. In predicting epidemics defined as a seasonal cumulative incidence of 100/10⁵ population, an epidemic threshold of 10 cases/10⁵ population/week performed well. Based on this same epidemic threshold, with a 6 week interval between crossing the epidemic threshold and population protection from a meningococcal vaccination campaign, an estimated 17 cases per event would be prevented by vaccination. Lowering the threshold increased the number of cases per event potentially prevented, as did shortening the response interval. If the interval was shortened to 4 weeks at the threshold of 10/10⁵, the number of cases prevented would increase to 54 per event.ConclusionsAccelerating time to vaccination could prevent more cases per event than lowering the threshold. Once the meningitis epidemic threshold is crossed, it is of critical importance that vaccination campaigns, where appropriate, are initiated rapidly.     

Epidemic group C meningococcal meningitis in Upper Volta, 1979

Group C meningococci were isolated during an epidemic of meningococcal meningitis which occurred between January and May 1979 in eastern Upper Volta, an area previously associated with endemic and epidemic group A disease. A total of 539 cases of meningitis, 55 of which were fatal, were reported, giving an attack rate of 517 cases per 100 000 inhabitants. Attack rates were higher for children under 15 years of age. Clinical and bacteriological data suggested that the group C meningococci were sulfonamide-resistant. The last meningococcal epidemic in Upper Volta occurred in 1970 and was nationwide. Epidemic cycles of group A meningococcal meningitis have occurred at 10-15 year intervals in the sub-Saharan region, raising concern that the current increase in activity may presage more wide-spread disease in the next dry season.     

Management of an outbreak of meningococcal meningitis in a Sudanese refugee camp in Northern Uganda

We describe an outbreak of meningitis at a Sudanese refugee camp in Northern Uganda that lasted over a year from February 1994. Some 291 cases occurred in a refugee population of 96860 (averaged over the year), an attack rate of 0.30%. The case fatality rate was 13.3%. From a small number of samples taken for culture N. meningitidis serogroup A, serotype 21:P1.9, clone III-1 was identified as the causative organism. The outbreak started in the camp's reception centre which had the highest attack rate. Spread from the reception centre was rapid and the epidemic reached its peak within 3 weeks. All of the cases amongst residents of the reception centre reported having had meningococcal vaccine before arriving at the camp and so were not immunized on arrival as would normally have been the case. Some 37 547 doses of meningococcal vaccine were used in a mass immunization campaign in February and March 1994. Following this the outbreak was declared over in August 1994 when no cases were registered for 2 consecutive weeks. However, following a massive and sudden influx of refugees a new epidemic peak occurred during February 1995. Many of these new refugees were also not immunized on arrival due to pressures of numbers. A follow-up immunization campaign then brought an end to the outbreak. Our experience confirms the effectiveness of timely and high-coverage immunization campaigns in controlling group A meningitis outbreaks amongst refugees in Africa.     

流脑A群多糖菌苗划片免疫九年流行病学效果观察

据预测1984年前后保定市为流脑大流行高峰年。为预防其出现,于1980~1984年对保定市区1~15岁儿童进行了两轮流脑多糖菌苗的按区划片免疫,接种率达80.01%。1985~1988年只对12~24月龄幼儿进行接种,接种率为97.15%。9年间免疫组观察833 333人发病4人,发病率为0.48/10万;对照组观察304 085人,发病25人,发病率为8.22/10万。菌苗保护率为94.16%,效果指数1:17.12。不仅有效地防止了保定市1984年大流行高峰年而且使1980~1988年连续9年流脑发病率维持在1/10万左右,是历史上最低水平。     

A+C群脑膜炎球菌多糖疫苗在C群流脑暴发中应急接种效果的研究

目的 报告A+C群脑膜炎球菌多糖疫苗(A+C群MPV)在C群流行性脑脊髓膜炎(流脑)暴发疫情中应急接种的安全性、免疫原性和保护效果.方法 在2002年广西来宾市发生C群流脑局部暴发接种A群MPV人群中约6周后应急接种A+C群MPV,观察接种对象局部和全身反应.选择疫点人群71人和非疫点人群43人于应急接种前和接种后1个月采血,用ELISA检测脑膜炎球菌C群和A群多糖抗体IgG.随访接种人群流脑发病情况至免疫后5年.结果 A+C群MPV应急接种率为97%,接种后未观察到严重不良反应.疫点人群、非疫点人群、应急接种前C群抗体阴性者和阳性者的C群流脑抗体阳性率为97.67%～100%,几何平均浓度(GMC)为30.81～37.44 μg/ml,各组人群抗体水平差异无统计学意义.流脑罹患率在及时接种学校(218.58/10万)比不及时接种学校(705.72/10万)减少69.02%.接种人群随访15 760人年未发现流脑临床确诊病例.结论 国产A+C群MPV应急接种可成功扑灭C群流脑暴发疫情,与A群MPV仅间隔6周接种仍然安全,对易感人群可诱导产生高水平的特异性抗体,对已有抗体者可显著提高抗体水平,保护效果至少持续5年.     

Reactive vaccination as a control strategy for pneumococcal meningitis outbreaks in the African meningitis belt: Analysis of outbreak data from Ghana

Streptococcus pneumoniae is increasingly recognised as an important cause of bacterial meningitis in the African meningitis belt. The World Health Organization sets guidelines for response to outbreaks of meningococcal meningitis, but there are no current guidelines for outbreaks where S. pneumoniae is implicated. We aimed to evaluate the impact of using a similar response to target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis belt. Here, we adapt a previous model of reactive vaccination for meningococcal outbreaks to estimate the potential impact of reactive vaccination in a recent pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using weekly line list data on all suspected cases over a period of five months. We determine the sensitivity and specificity of various epidemic thresholds and model the cases and deaths averted by reactive vaccination. An epidemic threshold of 10 suspected cases per 100,000 population per week performed the best, predicting large outbreaks with 100% sensitivity and more than 85% specificity. In this outbreak, reactive vaccination would have prevented a lower number of cases per individual vaccinated (approximately 15,300 doses per case averted) than previously estimated for meningococcal outbreaks. Since the burden of death and disability from pneumococcal meningitis is higher than that from meningococcal meningitis, there may still be merit in considering reactive vaccination for outbreaks of pneumococcal meningitis. More outbreak data are needed to refine our model estimates. Whatever policy is followed, we emphasize the importance of timely laboratory confirmation of suspected cases to enable appropriate decisions about outbreak response.     

Epidemic poliomyelitis in The Gambia following the control of poliomyelitis as an endemic disease. I. Descriptive findings.

An epidemic of type 1 poliomyelitis involving 305 cases occurred in The Gambia (estimated 1986 population, 768,995) from May through November 1986, following a 6-year period when only five cases were reported. Cases were identified by physician reporting during the epidemic and by a national village-to-village search conducted after the epidemic. The national attack rate was 40 cases per 100,000 people. Cases lived in all parts of the country except the capital, Banjul. The peak month of the epidemic was August (139 cases). The highest attack rate by year of age was in 1-year-old children (394 cases per 100,000 persons), and 75% of cases were 3 years of age or less. A vaccination coverage survey showed that 64% (95% confidence interval 60-68) of 1- to 2-year-old children were vaccinated with at least three doses of trivalent oral polio vaccine at the beginning of the epidemic. Fifty-seven cases became paralyzed more than 2 weeks after a national mass campaign in which 95% of children 1-7 years old were reported to have received a dose of trivalent oral polio vaccine. Experience in The Gambia shows that a several-year period of excellent control of endemic poliomyelitis by a vaccination program can be followed by a major epidemic and that a mass vaccination campaign may be only partially successful in ending the epidemic.     

The burden of hospitalizations for meningococcal infection in Spain (1997-2008)

All hospital discharges and deaths related to invasive meningococcal disease, meningococcal meningitis and meningococcemia in the general population from 1997 to 2008 in Spain were obtained. Among the 11,611 meningococcal infection related discharges 53% were meningococcal meningitis and 55% were meningococcemia. The annual hospitalization rate was 2.33, 1.23 and 1.29 cases per 100,000 for invasive meningococcal disease, meningococcal meningitis and meningococcemia, respectively. 846 deaths for invasive meningococcal disease, 235 for meningococcal meningitis and 605 for meningococcemia were reported. Although an important decrease in meningococcal infections related morbidity and mortality has occurred in the last twelve years in Spain, they still continue being major causes of hospitalization and death, especially in the children up to 2 years of age. Future preventive measures, such as vaccination with vaccines covering new conjugated serogroups (B and ACYW135), could further improve population health.     

Meningococcal meningitis in sub-Saharan Africa: the case for mass and routine vaccination with available polysaccharide vaccines

Endemic and epidemic group A meningococcal meningitis remains a major cause of morbidity and mortality in sub-Saharan Africa, despite the availability of the safe and inexpensive group A meningococcal polysaccharide vaccine, which is protective at all ages when administered as directed. Despite optimal therapy, meningococcal meningitis has a 10% fatality rate and at least 15% central nervous system damage. WHO's policy of epidemic containment prevents, at best, about 50% of cases and ignores endemic meningitis, which is estimated at 50,000 cases per year. The effectiveness of group A, C, W135, and Y capsular polysaccharides is the basis for recommending universal vaccination with group A meningococcal polysaccharide twice in infancy, followed by the four-valent vaccine in children aged two and six years. This could eliminate epidemic and endemic disease, prepare for the use of conjugates when they become available, and probably could have prevented the recent epidemics of groups A and W135 meningitis in Burkina Faso.     

江西省2004-2007年流行性脑脊髓膜炎流行病学特征分析

目的分析江西省流行性脑脊髓膜炎（流脑）流行病学特征,为预防和控制流脑提供依据。方法用描述流行病学方法,对江西省疾病监测信息管理系统报告的2004-2007年流脑流行趋势进行分析。结果江西省2004～2007年流脑发病率为0．069／10万-0．129／10万,平均发病率0．105／10万;病死率为2．2％-16．7％;1-4月为发病高峰;〈15岁儿童发病占总病例数的75．4％;学生发病占总病例数的57．5％;送检的病例标本中,检出C群脑膜炎球菌的占73．9％。结论应规范接种A群、A＋C群脑膜炎球菌疫苗,加强流脑监测和在校学生流脑的预防控制。     

江苏省正常人群A群流脑抗体水平及免疫成功率监测

目的:通过流脑流行前期人群A群流脑抗体水平、带菌率的监测和A群流脑多糖菌苗基础免疫成功率的监测,评价江苏省流脑多糖菌苗的接种状况、工作质量,以及人群A群流脑免疫水平。方法:采用ELISA法测定正常人群A群流脑血清抗体水平、A群流脑免疫成功率,以及采集咽拭子进行人群带茵情况调查。结果:2001-2002年流脑流行前期全省7个年龄组1152人中A群流脑抗体阳性率为89.5%,几何平均滴度(GMT)为1:16.6,其中2002年人群A群流脑抗体阳性率高于2001年,人群A群、C群流脑带茵率<1%。2003年A群流脑多糖菌苗基础免疫成功率为89.6%,GMT为1:17.5,抗体4倍增长率为88.0%。结论:江苏省正常人群A群流脑多糖菌苗基础免疫成功率较高,抗体水平具有保护作用,人群带菌率较低。     

Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997

Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the total cost of the campaign, materiel for injection and safety of injection 26%, vaccination staff 7%, and logistics 7%. The mean cost was 0.34 euro per administered dose and 0.64 euro per vaccinee. The mean cost per administered dose of meningococcal vaccine was 0.44 euro. The mean cost of preventive meningococcal immunization was not higher than the mean cost of meningococcal vaccination during mass emergency immunization campaigns in other countries. The addition of yellow fever antigen brought down the campaign mean cost by 0.11 euro and it allowed economies of scales. Direct unit costs per administered dose were higher when people were vaccinated through the outreach strategy (0.35 euro) than when fixed and mobile strategies were used (0.318 and 0.323 euro, respectively). Costs related to transportation and staff were proportionally higher for the outreach strategy. Direct unit costs per administered dose were higher when vaccinations were done in rural areas (0.32 euro) than when done in urban areas (0.31 euro). Direct unit costs increased when the size of target communities decreased (in communities with less than 100 people to vaccinate versus 0.38 euro in communities with more than 2,000 people to vaccinate). This study allowed us to set up a method to measure, describe and analyze the costs of a mass preventive campaign. It demonstrated the economic impact of using multiple antigens during a single preventive campaign.     

Mass vaccination campaign following community outbreak of meningococcal disease

During December 12-29, 1998, seven patients ages 2-18 years were diagnosed with serogroup C meningococcal disease in two neighboring Florida towns with 33,000 residents. We evaluated a mass vaccination campaign implemented to control the outbreak. We maintained vaccination logs and recorded the resources used in the campaign that targeted 2- to 22-year-old residents of the two towns. A total of 13,148 persons received the vaccinations in 3 days. Vaccination coverage in the target population was estimated to be 86% to 99%. Five additional cases of serogroup C meningococcal disease occurred in the community during the year after the campaign began, four in patients who had not received the vaccine. The cost of control efforts was approximately $370,000. Although cases continued to occur, the vaccination campaign appeared to control the outbreak. Rapid implementation, a targeted approach, and high coverage were important to the campaign's success.     

Early detection and response to meningococcal disease epidemics in sub-Saharan Africa: appraisal of the WHO strategy

OBJECTIVE: To assess the sensitivity, specificity and predictive value positive of the WHO threshold strategy for detecting meningococcal disease epidemics in sub-Saharan Africa and to estimate the impact of the strategy on an epidemic at district level. METHODS: Data on meningitis cases at the district level were collected weekly from health ministries, WHO country and regional offices, and nongovernmental organizations in countries where there were epidemics of meningococcal disease in 1997. An epidemic was defined as a cumulative district attack rate of at least 100 cases per 100,000 population from January to May, the period of epidemic risk. The sensitivity, specificity and predictive value positive of the WHO threshold rate were calculated, and curves of sensitivity against (1 - specificity) were compared with alternatively defined threshold rates and epidemic sizes. The impact of the WHO strategy on a district epidemic was estimated by comparing the numbers of epidemic cases with cases estimated to have been prevented by vaccination. FINDINGS: An analysis was made of 48 198 cases reported in 174 districts in Benin, Burkina Faso, the Gambia, Ghana, Mali, Niger, and Togo. These cases were 80.3% of those reported from Africa to WHO during the 1997 epidemic period. District populations ranged from 10,298 to 573,908. The threshold rate was crossed during two consecutive weeks in 69 districts (39.7%) and there were epidemics in 66 districts (37.9%). Overall, the sensitivity of the threshold rate for predicting epidemics was 97%, the specificity was 95%, and the predictive value positive was 93%. Taken together, these values were equivalent or better than the sensitivity, specificity and predictive value positive of alternatively defined threshold rates and epidemics, and remained high regardless of district size. The estimated number of potential epidemic cases decreased by nearly 60% in the age group targeted for vaccination in one district where the guidelines were followed in a timely manner. CONCLUSION: The use of the WHO strategy was sensitive and specific for the early detection of meningococcal disease epidemics in countries of sub-Saharan Africa during 1997 and had a substantial impact on a district epidemic. Nevertheless, the burden of meningococcal disease in these countries remains formidable and additional control measures are needed.     

Evolution of meningococcal disease in the community of Madrid. Effectiveness of antimeningococcal A+C vaccination

BACKGROUND: In 1997 (between 22 September and 14 November) an A + C meningococcal mass vaccination campaign was carried out in Madrid, targeting the age group of from 18 months to 19 years of age, in the face of an increase in the number of cases of meningococcal disease caused by serogroup C occurring in the 1996-97 season. This study forms a part of the impact assessment of that campaign. METHODS: The evolution of the meningococcal disease, by means of the comparison of rates of incidence; and the efficacy of the vaccination campaign was determined after one year (1997-98 season) and after two years (1997-98 and 1998-99 seasons) of monitoring. The vaccine efficacy has been calculated as [1-(Incidence rate in vaccinated/Incidence rate in unvaccinated)]* 100. RESULTS: A significant drop was registered in the incidence of serogroup C meningococcal disease on comparing the 1997-98 and 1998-99 seasons with the epidemic season (1996-97). The vaccine efficacy after two years of monitoring subsequent to the vaccination campaign was 76.9% for the global population between 18 months and 19 years of age and 88.5% in the group of vaccinated individuals between 15 and 19 years of age. CONCLUSIONS: The vaccine efficacy obtained is compatible with that described in the relevant literature. The significant reduction in the incidence of meningococcal disease caused by serogroup C was due to the vaccine efficacy obtained.     

Investigating the aetiology of and evaluating the impact of the Men C vaccination programme on probable meningococcal disease in England and Wales

The aims were to (1) investigate the aetiology of probable meningococcal disease, where a clinical diagnosis is made in the absence of laboratory data, and (2) evaluate the impact of the Men C vaccination programme in England and Wales. Multiple linear regression analyses were carried out using data reported to Enhanced Surveillance of Meningococcal Disease (ESMD) and laboratory reports of isolates of organisms causing symptoms that mimic meningococcal disease. Confirmed meningococcal disease appeared to be a significant predictor of probable disease. Thus, an additional reduction in meningococcal disease attributable to the serogroup C vaccination campaign was evident in probable disease over and above that observed in confirmed cases alone. Enteroviruses were a significant contributor to cases of probable meningitis and influenza appeared to be a significant contributor to probable cases of septicaemia. This analysis confirms the success seen following the Men C vaccination campaign and gives an indication of the aetiologies of other causes of probable meningitis and septicaemia reported to ESMD.     

Comparison of cost-effectiveness of preventive and reactive mass immunization campaigns against meningococcal meningitis in West Africa: a theoretical modeling analysis

For epidemic meningitis control in sub-Saharan Africa, the World Health Organization recommends a strategy of emergency vaccination with meningococcal A + C polysaccharide vaccine when epidemic thresholds are exceeded. An alternative strategy for areas without effective surveillance systems is mass preventive campaigns before outbreaks occur. A model was formulated to simulate epidemics and to compare the cost-effectiveness of these two strategies for the district of Matam, Senegal, where an actual preventive campaign was performed during 1997. The preventive strategy prevented 59% of the cases compared to 49% for the emergency strategy. The cost per case prevented was US$59 for the preventive strategy and US$133 for the reactive strategy, and the preventive strategy saved US$0.20 per habitant. Preventive meningococcal vaccination through mass campaigns prevented more outcomes at a lower cost, provided that the occurrence of an epidemic could be predicted within 3 years and that the vaccination coverage rates for the preventive and standard strategies were > 70% and < 94%, respectively. Sub-Saharan African countries without effective surveillance systems should consider mass preventive campaigns while awaiting an affordable conjugate vaccine.     

Meningococcal disease in the Netherlands: media hype, but not an epidemic

An outbreak of meningococcal disease caused by Neisseria meningitidis C, type 2a recently occurred in the Dutch province of West-Brabant. Five children were affected and two of these died. The Outbreak Management Team decided to start a local vaccination campaign with a meningococcal group C conjugate vaccine. The publicity surrounding these cases of meningococcal disease led to much anxiety throughout the Netherlands. Despite parent's concerns, there is nothing to indicate the presence of an epidemic.     

Invasive meningococcal disease and travel

The epidemiology of invasive meningococcal disease varies geographically and in time and the risk of acquiring the disease varies regionally, as well as with living conditions and behavior. An area, in which meningococcal disease outbreaks have frequently occurred, is the "African meningitis belt", where epidemics of meningococcal disease with a peak incidence as high as 100-800/100,000 population/year have been reported. Another risk factor is mass gatherings including the Islamic pilgrimage to Makkah (Mecca), where outbreaks of meningococcal disease have repeatedly occurred. The latest outbreaks occurred during the Hajj pilgrimages of 2000 and 2001, when a shift from serogroup A disease to serogroup W135 occurred. Vaccination against serogroups A, C, W-135 and Y with novel conjugate vaccines may help protect individuals and reduce the spread of bacterial carriage and disease. Individuals who should be vaccinated include travelers to epidemic or hyperendemic areas (as identified by international health authorities), travelers for Umra or Hajj (Hajj pilgrims), travelers to high risk countries or regions (African meningitis belt) during the dry season or countries in sub-Saharan Africa outside the meningitis belt (where outbreak of meningitis has been reported in the preceding 2-3 years), military recruits or deployed military personnel, immunocompromized travelers and high school and college students. This review presents the global epidemiology of meningococcal disease, and discusses prophylaxis options including meningococcal ACWY vaccines.     

Control of a community outbreak of group C meningococcal meningitis in Corupá, Santa Catarina State, Brazil, based on rapid and effective epidemiological surveillance and immunization

In 2001, an outbreak of eight cases of meningococcal disease within seven days occurred in a small municipality in northern Santa Catarina State, Brazil. All cases occurred in adolescents and young adults, corresponding to an attack rate of 367.5 cases per 100,000 inhabitants in this population group. Laboratory tests identified serogroup C meningococcus in three out of eight cases. This led to vaccination of all inhabitants in the municipality over two years of age against serogroup C meningococcus -- an outbreak control strategy recommended by the Brazilian Ministry of Health. The absence of new cases during a 12-month period after vaccination indicates the importance of this type of intervention in disease control.