a Epicentre, 8 rue Saint-Sabin, 75011 Paris, France.
b Direction Générale de la Santé, Ministère de la Santé, BP 336, Lomé, Togo.
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Abstract |
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Methods Meningitis cases recorded for 19901997 in health centres of northern Togo were reviewed. Weekly and annual incidences were determined for each district. Ability of different weekly incidence thresholds to detect outbreaks was assessed according to sensitivity, specificity, and positive and negative predictive values. The number of cases potentially prevented by reactive vaccination in 1997 was calculated for each threshold.
Results Outbreaks occurred in 19951996 and in 19961997. The WHO-recommended threshold had good specificity but low sensitivity. Thresholds of 10 and 7 cases per 100 000 inhabitants in one week had sensitivity and specificity of 100% and increased the time available for intervention by more than one or two weeks, respectively. A maximum of 65% of cases could have been prevented during the 1997 epidemic, with up to 8% fewer cases prevented for each week of delay in achieving vaccine coverage.
Conclusions In northern Togo, thresholds of 7 or 10 cases per 100 000 inhabitants per week were excellent predictors of meningitis epidemics and allowed more time for a reactive vaccination strategy than current recommendations.
Keywords Meningitis, meningococcal, epidemic, threshold, vaccination, Africa, sensitivity, specificity
Accepted 3 March 2000
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Introduction |
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Based on meningitis case data from Burkina Faso (1979 1984), Moore et al.4 proposed the use of a weekly meningitis incidence rate of 15 cases per 100 000 inhabitants, averaged over 2 consecutive weeks, as a threshold to predict the subsequent occurrence of a meningitis epidemic and a lower alert threshold of 5 cases per 100 000 inhabitants per week in districts contiguous to areas already declared epidemic. In 1995, WHO recommended application of these thresholds for control of epidemic meningococcal disease in the African meningitis belt3 and they have been used since then.57 Experience has shown, however, that under field conditions, the time required to decide upon and organize mass vaccination campaigns may delay interventions, resulting in a limited overall impact.6,7
The northern part of Togo, at the southern edge of the African meningitis belt, suffered a major group A meningococcal meningitis epidemic in 199619978 as a wave of epidemics swept through the region.9 This study, with data from northern Togo, assesses the validity of the currently recommended threshold and studies other thresholds that might allow an earlier detection of meningococcal meningitis epidemics and thereby increase the impact of reactive mass vaccination campaigns.
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Methods |
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Meningitis incidence rates were calculated for each district by dividing the number of new cases occurring in the area per unit of time (week or year) by the annually adjusted population of the area. For this study, the year span was defined as 1 August through 31 July of the following year in order to include a complete meningitis season (DecemberMay).
Definition of an epidemic
An epidemic year was retrospectively defined in a district by a yearly meningitis incidence of 100 cases per 100 000 inhabitants.3 The peak of the epidemic was defined as the week with the maximum weekly incidence. Threshold analyses were repeated for other hypothetical definitions of an epidemic (70, 80 and 90 cases/100 000 inhabitants/year).
Threshold study
Weekly meningitis incidences between 2 and 25 cases/100 000 inhabitants were investigated as potential thresholds for predicting the emergence of an epidemic during the corresponding year. The WHO recommended threshold of 15 cases/100 000 inhabitants averaged over 2 consecutive weeks was also tested.
Estimates of the sensitivity, specificity, positive predictive value and negative predictive value of these thresholds were calculated by determining which district crossed, at least once, the given threshold and experienced an epidemic during the same year. The sensitivity is the probability that the threshold was crossed during an epidemic year; the specificity is the probability that the threshold was not crossed during a non-epidemic year; the positive predictive value is the probability that there was an epidemic if the threshold had been crossed at least once; the negative predictive value is the probability that there was no epidemic if the threshold had never been crossed during a given year.
The time available for intervention was also studied for the various thresholds. It was calculated as the number of weeks elapsed between the first week the threshold was crossed and the week of the epidemic peak. Thresholds were analysed for their ability to predict the occurrence of an epidemic within the year during which they were crossed.
Impact study
The number of cases which may have been prevented by a mass vaccination campaign during the 19961997 epidemic in the Région des Savanes was estimated using a method described by Pinner et al.11 The number of meningitis cases which would have occurred in the absence of a vaccination campaign was estimated on the basis of the weekly meningitis incidence, the meningitis vaccination coverage obtained during this epidemic and the vaccine effectiveness. The number of cases potentially prevented was then estimated through different scenarios, depending on the threshold and vaccination strategy used. This method assumes that vaccination does not interfere with meningococcal carriage or transmission,7,11 an assumption that seems valid for group A meningococcal polysaccharide vaccines in African populations.12
Vaccine coverage for the study area was assumed to be 0% prior to the 19961997 epidemic and was calculated after the epidemic by dividing the number of doses administered to individuals in each district during this epidemic by the 1997 population of the district. Vaccine coverage was stratified according to age (014 and 15 years). Vaccine efficacy was assumed to be 85%13 and time for seroconversion was set at one week after vaccination. After the threshold was crossed, a theoretical time-frame of a week was initially allocated for gathering and analysing data, ordering vaccines, organizing the campaigns and achieving vaccination objectives. The influence of delay in the initiation of vaccination on the number of cases which may have been prevented was studied with a sensitivity analysis allowing the time to achieve vaccination objectives to vary from 2 to 8 weeks. Vaccine coverage was either the actual coverage achieved by the mass campaign in Togo or a theoretical coverage of 85% of the entire population.
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Results |
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Thresholds below 7 cases/100 000 inhabitants/week resulted in sensitivity and negative predictive value of 100%, but low to medium specificity and positive predictive value, whereas thresholds over 15 cases/100 000 inhabitants/week resulted in lower sensitivity and negative predictive value, but specificity and positive predictive value of 100%.
Results were identical for an epidemic defined as 90 cases/ 100 000 inhabitants/year. Due to the high endemic rates of meningitis in Tone district in all years (Table 1
), use of lower annual incidences to define an epidemic year resulted in lower sensitivity for all thresholds tested, as years are declared epidemic in spite of low weekly incidences.
Time available for intervention
The mean time elapsed between the threshold and the peak of the epidemic ranged from 2.3 weeks, after surpassing 25 cases/ 100 000 inhabitants/week, to a maximum of 8.6 weeks with a threshold of 2 cases/100 000 inhabitants in one week. The threshold of 10 cases/100 000 inhabitants/week left 4.2 weeks for intervention before the epidemic peak whereas 7 cases/ 100 000 inhabitants/week left 5.4 weeks on average (Table 3).
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Discussion |
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Meningitis incidence thresholds of 7 and 10 cases/100 000 inhabitants/week both achieved 100% sensitivity and specificity, accurately predicting all epidemics in the four districts of northern Togo over the period 19901997. In contrast, the threshold of 15 cases/100 000 inhabitants/week in a district, averaged over 2 consecutive weeks, predicted meningitis epidemics with excellent specificity and positive predictive value but failed to detect one epidemic in Tone district in 19951996 (population >225 000), resulting in a lower sensitivity and negative predictive value, as previously shown.4 This may serve to illustrate the lower sensitivity of this threshold in larger populations. In this study, we chose to work with the actual district population figures, rather than dividing them arbitrarily into smaller units, in order to test thresholds in the real-life situations faced by district health officers.
Lower thresholds also allowed earlier detection of epidemics. In this study, thresholds of 7 and 10 cases/100 000 inhabitants/ week offer on average 2.4 and 1.2 weeks, respectively, more time to achieve vaccination coverage than current recommendations. The time elapsed between epidemic threshold and peak is critical in a strategy based on reactive mass vaccination.6 The reactive strategy must allow time to collect and analyse field data (usually through a surveillance system), decide on mass vaccination, order the vaccines, and organize and implement the vaccination campaign. Our baseline model allowed just one week for these activities but field experience shows that it takes at least 23 weeks to mount such a response. In our study, each week of delay in completing the vaccination campaign resulted in a 38% decrease in the number of cases prevented, similar to what was found using meningitis data from Ghana.7 Therefore any strategy that increases the time available for a response should be seriously considered. Woods et al. have demonstrated that knowledge of meningitis epidemics in neighbouring countries could provide an earlier alert.7 Although the Région des Savanes borders Bénin, Burkina Faso and Ghana, data from these countries were not available to us at the time of the study.
The potential impact of reactive mass vaccination is inherently limited by vaccination coverage achieved, as this study illustrates, and by the efficacy of the polysaccharide vaccine.1416 In the model presented here, even with a highly sensitive threshold and ideal conditions where 85% of the population can be vaccinated within one week of crossing the threshold, a maximum of 65% of the meningitis cases could have been prevented during the 19961997 epidemic in Togo. In reality, an estimated 49% or 3419 cases of meningitis were prevented, a figure which still fully justifies the vaccination campaign. Figure 4 shows that, for a given vaccination coverage, the use of the lower threshold (7 cases/100 000 inhabitants/week) allows one more week for intervention than the currently recommended threshold to achieve the same impact (proportion of cases prevented). Therefore, the additional time provided by a lower threshold can make a real difference in the potential impact of a vaccination campaign. These findings illustrate the difference between a theoretical approach based only on sensitivity and specificity and a pragmatic approach that accounts for the time necessary to implement epidemic control measures. Although our results suggest that strict adherence to WHO guidelines would allow the prevention of a similar proportion of meningitis cases as use of a lower threshold, the delay engendered by waiting for that higher (more specific and less sensitive) threshold may actually set back the whole reponse to the epidemic, thus reducing the number of cases prevented.
The results of our study are based on the number of cases recorded in the clinic logbooks at the peripheral level, giving the best available representation of the actual number of cases. In an operational context, however, decisions must usually be made using information from surveillance systems. This will inevitably be less efficient, as the timeliness and sensitivity of case detection can vary widely.4 If reporting from health facilities is incomplete or delayed, thresholds will be apparently crossed later in the epidemic and interventions based on surveillance data will be delayed. This underlines the need for awareness of surveillance system performance, for improving the quality and timeliness of meningitis surveillance and for undertaking field investigation whenever an outbreak is suspected. Incomplete or delayed reporting of cases to district surveillance officers is a further argument for using as sensitive a threshold as possible for detection of meningitis outbreaks.
This study is limited by the small area studied. Despite the large amount of data collected, the number of observations available for the threshold study was 28 district-years (four districts over 7 years), resulting in wide confidence intervals on the estimates of performance characteristics. The small data set precluded the comparison of performance characteristics for epidemic and non-epidemic years. The study area is located at the southern edge of the meningitis belt and may not be representative of the entire region. As characteristics of meningitis epidemics may vary from one area to another, further studies are needed in other sub-Saharan Africa countries. In addition, study of thresholds at a sub-district level may provide further useful information. Recommendations regarding detection of meningitis outbreaks in small populations using absolute numbers of cases (e.g. doubling of number of cases over 3 weeks or comparison with previous years)3 could be tested and validated.
At the present time, the reactive vaccination strategy is the only one possible for most regions of the meningitis belt due to limited resources.1416 Preventive mass vaccination with the polysaccharide vaccine has been discussed as an alternative17 but this approach would suffer from the same flaws as the reactive strategy, i.e. the absence of herd immunity12 and a moderate vaccine efficacy. In addition, the short duration of protection offered by the polysaccharide vaccine13 and the unpredictability of meningitis epidemics has so far limited its potential usefulness. Where resources permit, a preventive strategy could be considered for areas with very high endemic rates of disease. Preventive vaccination would be a suitable alternative with a vaccine inducing long-term immunity in children and herd immunity in the populations vaccinated. Meningococcal conjugate vaccines currently under development seem to have these characteristics and represent the best hope for the improvement of meningitis epidemic control in Africa, provided that they are affordable for countries with limited resources.
In the meantime, efforts must continue to improve the impact of mass vaccination in the face of devastating meningitis epidemics. Avenues to pursue include improving surveillance systems and encouraging international collaboration. Use of lower, more sensitive, epidemic thresholds should be preferred over specific ones to enable quicker action and the time required to mount an appropriate and comprehensive response should be accounted for.18 New recommendations concerning meningitis epidemic thresholds have been drafted, taking into consideration these and other important elements.19
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Acknowledgments |
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References |
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2 Moore PS. Meningococcal meningitis in sub-Saharan Africa: a model for the epidemic process. Clin Infect Dis 1992;14:51525.[ISI][Medline]
3 World Health Organization. Control of Epidemic Meningococcal Disease WHO Practical Guidelines. Lyon: Ed. Fondation Marcel Mérieux, 1995.
4 Moore PS, Plikaytis BD, Bolan GA et al. Detection of meningitis epidemics in Africa: a population-based analysis. Int J Epidemiol 1992; 21:15562.[Abstract]
5 Varaine F, Caugant DA, Riou J-Y et al. Meningitis outbreaks and vaccination strategy. Trans R Soc Trop Med Hyg 1997;91:37.[ISI][Medline]
6 Veeken H, Ritmeijer K, Hausman B. Priority during a meningitis epidemic: vaccination or treatment? Bull World Health Organ 1998; 76:13541.[ISI][Medline]
7 Woods CW, Armstrong G, Sackey SO et al. Emergency vaccination against epidemic meningitis in Ghana: implications for the control of meningococcal disease in West Africa. Lancet 2000;355:3033.[ISI][Medline]
8 Aplogan A, Batchassi E, Yakoua Y et al. Une épidémie de méningite à méningocoque dans la région des Savanes au Togo en 1997: investigation et stratégies de contrôle. Santé 1997;7:38490.
9 WHO. Meningitis in the WHO African RegionUpdate, January-April 1997. Wkly Epidemiol Rec 1997;72:131.
10 Palmore JA, Gardner RW. Measuring Mortality, Fertility and Natural Increase. A Self Teaching Guide to Elementary Measures, 5th Edn. Honolulu: East West Center Ed., 1994.
11 Pinner RW, Onyango F, Perkins BA et al. Epidemic meningococcal disease in Nairobi, Kenya, 1989. The Kenya/Centers for Disease Control (CDC) meningitis study group. J Infect Dis 1992;166:35964.[ISI][Medline]
12 Hassan-King MKA, Wall RA, Greenwood BM. Meningococcal carriage, meningococcal disease and vaccination. J Infect 1988;16: 5559.[ISI][Medline]
13 Reingold AL, Hightower AW, Bolan GA et al. Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet 1985;2:11418.[ISI][Medline]
14 Kaninda AV, Varaine F, Henkens M, Paquet C. Meningococcal vaccine in sub-Saharan Africa [comment]. Lancet 1997;350:1708.
15 Perkins BA, Broome C, Rosenstein NE, Schuchat A, Reingold AL. Meningococcal vaccine in sub-Saharan Africa [comment]. Lancet 1997;350:1708.
16 Wenger J, Tikhomirov E, Barakamfitiye D, Bele O, Heymann DL. Meningococcal vaccine in sub-Saharan Africa [comment]. Lancet 1997;350:1709.[Medline]
17 Robbins JB, Towne DW, Gotschlich EC, Schneerson R. Loves labours lost: failure to implement mass vaccination against group A meningococcal meningitis in sub-Saharan Africa. Lancet 1997;350:88082.[ISI][Medline]
18 Lewis R, Varaine F, Belanger F, Nathan N, Diarra L. Control of meningococcal disease in West Africa (Letter). Lancet 2000;355: 118586.[Medline]
19 Consensus meeting on epidemic thresholds for meningococcal meningitis in Africa. Wkly Epidemiol Rec 2000;(In Press).