Effectiveness of incidence thresholds for

detection and control of meningococcal

meningitis epidemics in northern Togo
Anne-Valérie Kaninda François Belanger Rosamund Lewis Essosolem BatchassiAristide
Aplogan Yénou Yakoua Christophe Paquet
International Journal of Epidemiology, Volume 29, Issue 5, 1 October 2000, Pages 933–
940, https://doi.org/10.1093/ije/29.5.933
Published:

01 October 2000

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Abstract
Background Early outbreak detection is necessary for control of meningococcal meningitis
epidemics. A weekly incidence of 15 cases per 100 000 inhabitants averaged over 2 consecutive
weeks is recommended by the World Health Organization (WHO) for detection of meningitis
epidemics in Africa. This and other thresholds are tested for ability to predict outbreaks and
timeliness for control measures.
Methods Meningitis cases recorded for 1990–1997 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 1995–1996 and in 1996–1997. 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.
Meningitis, meningococcal, epidemic, threshold, vaccination, Africa, sensitivity, specificity
Topic:

 meningitis
 meningococcal meningitis
 togo
 vaccination
 vaccines
 world health organization
 epidemic
Issue Section:
Original Article

Meningococcal meningitis, caused by the bacterium Neisseria meningitidis, is a public health

priority in the sub-Saharan region of Africa known as the ‘meningitis belt’.1 In this area,
meningococcal meningitis is endemo-epidemic, with tens of thousands of cases and thousands of
deaths reported during epidemic years.1–3 The strategy currently recommended by the World
Health Organization (WHO) to control meningococcal meningitis epidemics is based upon
therapeutic case management and mass vaccination with polysaccharide vaccine at the beginning
of an epidemic.3 As seasonal variations in the number of meningitis cases are observed in the
meningitis belt with an annual increase at the end of the dry season (December–April), it is
necessary to identify a threshold which is generally exceeded at the beginning of an epidemic but
not during endemic cycles.

Based on meningitis case data from Burkina Faso (1979– 1984), Moore et al.4proposed 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.5–7 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 1996–19978 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.

Methods

Meningitis incidence
The study took place in the Région des Savanes, in northern Togo, which is divided into
four préfectures (districts)—Tone, Oti, Kpendjal and Tandjoaré (Figure 1).
Clinic logbooks of health-care facilities of the study area were reviewed for cases of meningitis
which occurred between 1 August 1990 and 31 July 1997. A case was defined as a person
diagnosed with meningitis as written in the clinic logbook by the consulting physician or nurse.
The date of presentation to the health centre was considered to be the date of onset. Age, sex and
residence were recorded for each case. Population figures were determined for each year 1990–
1997 from a 1996 census conducted in the Région des Savanes (source: Direction Régionale de
la Santé des Savanes) and retrospectively adjusted for a 3% annual growth rate.10

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 (December–May).

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
1996–1997 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 1996–1997 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 (0–14 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.

Results
Descriptive epidemiology
The 1997 population of the study area was estimated to be 550 524 people (82 708 in Tandjoaré,
104 511 in Kpendjal, 127 567 in Oti and 235 738 in Tone). Mean population density is 63
inhabitants/km2. From August 1990 through July 1997, 5562 meningitis cases were counted in
the clinic logbooks of the health facilities, among which 4952 (89%) reported a residence in the
Région des Savanes. The weekly meningitis incidence in the region is presented in Figure 2.

Annual meningitis incidence for each district is presented in Table 1. From 1990 to 1995, no
epidemic was noted. In non-epidemic years, the incidence ranged from 4 to 86 cases/ 100 000
inhabitants/year with a mean of 35 and a median of 27. An epidemic occurred in early 1996 in
Tone district with an annual incidence of 168 cases/100 000 inhabitants. During this epidemic,
the maximum weekly incidence was 14.9 cases/ 100 000 inhabitants. In early 1997, another
epidemic occurred in all four districts of the Région des Savanes, accounting for 3590 cases
between 2 December 1996 and 1 June 1997. Overall annual incidence was 652 cases/100 000
inhabitants, varying from 154 in Oti district to 1135 in Tone. The epidemic threshold of 15
cases/100 000 inhabitants averaged over 2 weeks was exceeded in Tone during the first week of
1997 and the alert threshold of 5 cases/100 000 inhabitants/week was exceeded in Kpendjal
during week 2, in Oti during week 5 and in Tandjoaré during week 6.

Performance of epidemic thresholds

Crossing a threshold of 15 cases/100 000 inhabitants/week averaged over 2 consecutive weeks
yielded both specificity and positive predictive value of 100% for the prediction of an epidemic
(≥100 cases per 100 000 inhabitants) in a district during a given year. Sensitivity was 80% and
negative predictive value was 96% (Table 2). Results were exactly the same when testing a
threshold of 15 cases/100 000 inhabitants/week calculated over one week only.

Thresholds between 7 and 10 cases/100 000 inhabitants/ week calculated over one week in a
district resulted in sensitivity, specificity, positive and negative predictive values of 100%.

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).

Impact of the 1997 mass vaccination campaign

A serogroup A meningococcal meningitis epidemic occurred in the Région des Savanes8 from
December 1996 through May 1997, accounting for 3590 cases. Mass vaccination campaigns
were organized and a total of 346 469 doses of vaccine were administered in the four districts in
February 1997.8 Vaccine coverage in the four districts ranged from 58% to 69%, yielding a
weighted average administrative coverage for the region of 63%. The 1996–1997 epidemic curve
and a projection of the curve, had there been no vaccination during this epidemic, are presented
in Figure 3. According to the model, 49% (3419) of the projected cases were prevented by the
vaccination campaign. If the WHO recommendations had been strictly followed (vaccination
following a 2-week average of 15 cases/100 000 inhabitants/week for the first district and 5
cases/100 000 inhabitants/week for subsequent districts), 65% (4549) of the cases could have
been prevented by a vaccination campaign covering 85% of the population and completed by the
end of the second week of 1997 in Tone, the third week in Kpendjal, the sixth week in Oti and
the seventh week in Tandjoaré district. Using a single threshold of 7 cases/100 000
inhabitants/week in a district, 66% (4657) of the cases could have been prevented if 85% vaccine
coverage had been achieved by the end of the first week of 1997 in Tone and Kpendjal, the sixth
week in Oti and the seventh week in Tandjoaré district.

The effect of time needed to achieve vaccination on the proportion of cases prevented is
presented in Figure 4. For each week of delay, 3% to 8% fewer cases could be prevented and for
each drop in vaccine coverage of 10%, approximately 5% fewer cases are prevented. In order to
prevent a minimum of 60% of cases with an 85% vaccine coverage in the Région des Savanes,
vaccination should be achieved within 3.5 weeks after the threshold of 7 cases/100 000
inhabitants/week is crossed or within 2.5 weeks with WHO guidelines. To achieve the same
impact, the lower threshold would have provided one extra week to plan a response.

Discussion

In the management of meningococcal meningitis epidemics, time is of the essence. It is

imperative to detect an impending epidemic and institute control measures as early as possible if
large numbers of cases and deaths are to be prevented. In Togo, the 1997 meningitis epidemic
spread rapidly. This study shows that, following detection of an epidemic, the time available for
intervention and the vaccination coverage achieved are critical to the success of the reactive
vaccination strategy recommended for Africa by the WHO. Our findings confirm the validity of
the threshold approach but questions are raised as to whether the currently recommended
threshold is the most appropriate one.

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 1990–1997. 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
1995–1996 (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 2–3 weeks to mount such a response. In our study, each
week of delay in completing the vaccination campaign resulted in a 3–8% 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.14–16 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 1996–1997 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.14–16Preventive 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.18New recommendations
concerning meningitis epidemic thresholds have been drafted, taking into consideration these and
other important elements.19

Table 1
Annual meningitis incidence, Région des Savanes, northern Togo, 1990–1997

Meningitis incidence per district (no. of meningitis cases/100 000

inhabitants/year)

Year Kpendjal Oti Tandjoaré Tone

Source: clinic logbooks from the Région des Savanes.

1990–
1991 15 8 26 58

1991–
1992 22 7 29 70

1992–
1993 23 4 50 72
 Meningitis incidence per district (no. of meningitis cases/100 000
inhabitants/year)

Year Kpendjal Oti Tandjoaré Tone

1993–
1994 27 9 28 81

1994–
1995 23 17 51 86

1995–
1996 33 20 54 168

1996–
1997 347 154 197 1135

View Large

Table 2
Test characteristics of weekly meningitis incidence as predictor of meningitis
epidemics, northern Togo, 1990–1997

No. of
times the Positive Negative
Epidemic threshol predictiv predictiv
threshold d was e value e value
(cases/100 000 crossed Sensitivit Specificit (%) (%)
inhabitants/week) in a y (%) y (%) (95% (95%
districta (95% CI) (95% CI) CI) CI)

a 28 units of observation: 4 districts × 7 years of observation per district.

bResults are the same for an incidence of 15 cases/100 000 inhabitants/week during one week or
averaged over 2 consecutive weeks, and when the 2-week average is used for the first district in
combination with the alert threshold of 5 cases/100 000 inhabitants/week for the remaining
districts.
 No. of
times the Positive Negative
Epidemic threshol predictiv predictiv
threshold d was e value e value
(cases/100 000 crossed Sensitivit Specificit (%) (%)
inhabitants/week) in a y (%) y (%) (95% (95%
districta (95% CI) (95% CI) CI) CI)

2 24 100 17 21 100

(46.3, (5.7, (7.9, (39.6,

100.0) 39.5) 42.7) 100.0)

5 8 100 87 62 100

(46.3, (65.3, (25.9, (80.0,

100.0) 96.6) 89.8) 100.0)

7 5 100 100 100 100

(46.3, (82.2, (46.3, (82.2,

100.0) 100.0) 100.0) 100.0)

10 5 100 100 100 100

(46.3, (82.2, (46.3, (82.2,

100.0) 100.0) 100.0) 100.0)

15b 4 80 100 100 96

(29.9, (82.2, (39.6, (76.9,

98.9) 100.0) 100.0) 99.8)

20 4 80 100 100 96

(29.9, (82.2, (39.6, (76.9,

98.9) 100.0) 100.0) 99.8)
 No. of
times the Positive Negative
Epidemic threshol predictiv predictiv
threshold d was e value e value
(cases/100 000 crossed Sensitivit Specificit (%) (%)
inhabitants/week) in a y (%) y (%) (95% (95%
districta (95% CI) (95% CI) CI) CI)

25 3 60 100 100 92

(17.0, (82.2, (31.0, (72.5,

92.7) 100.0) 100.0) 98.6)

View Large

Table 3
Time elapsed between threshold and peak during the 1996–1997 meningitis epidemic,
Région des Savanes, northern Togo

Epidemic threshold (cases/100 000 Average time between threshold and 95%
inhabitants/week) epidemic peak (weeks) CIa

a Confidence interval calculated with the t distribution.

b Averaged over 2 consecutive weeks.

(5.0,
2 8.6 12.2)

(3.3,
5 5.4 7.5)

(3.3,
7 5.4 7.5)

(1.2,
10 4.2 7.2)
Epidemic threshold (cases/100 000 Average time between threshold and 95%
inhabitants/week) epidemic peak (weeks) CIa

(0.1,
15 4.0 7.9)

(–0.9,
15 b 3.0 6.9)

(–1.3,
20 2.5 6.3)

(–1.7,
25 2.3 6.2)

View Large

Figure 1

View largeDownload slide

Districts of Tone, Kpendjal, Tandjoaré and Oti, Région des Savanes, northern Togo

Figure 2

View largeDownload slide

Meningitis weekly incidencea in the Région des Savanes (a), and in each district (b, c, d, e), northern Togo,
1990–1997

Source: clinic logbooks from the Région des Savanes.

a
In the four districts (b, c, d, e) the incidence is truncated at 20 cases/100 000 inhabitants/week.

Figure 3

View largeDownload slide

Model of the impact of mass vaccination on the 1996–1997 meningitis epidemic in the Région des Savanes,
northern Togo
——–actual meningitis cases recorded (source: Direction Régionale de la Santé, Région des Savanes)

— —projected number of cases in the absence of vaccination

------projected number of cases if 85% vaccine coverage achieved after passing threshold of 7 cases/100 000
inhabitants/week

▪period when mass vaccination campaign was implemented

Figure 4

View largeDownload slide

Potential impact of mass vaccination according to threshold strategy and lag time before vaccination.
Meningitis epidemic, northern Togo, 1996–1997

Proportion of cases potentially prevented according to the number of weeks elapsed, if vaccination had been
initiated after the incidence in a district reached or exceeded:

--▴ -- 7 cases/100 000 inhabitants/week; vaccination coverage 85%

--♦--7 cases/100 000 inhabitants/week; vaccination coverage 63% (achieved in Togo in 1996–1997)

--○--15 cases/100 000 inhabitants/week averaged over 2 weeks; vaccination coverage 85%

--▪--15 cases/100 000 inhabitants/week averaged over 2 weeks; vaccination coverage 63%

This study has been funded by Médecins Sans Frontières. We wish to thank Dr Kombate, Dr
Aleki (Togo Ministry of Health), the health workers of the Région des Savanes and Médecins
Sans Frontières for their collaboration. We also wish to thank Dr Brian Greenwood for reviewing
the manuscript.

References
1
Lapeyssonie L. La méningite cérébro-spinale en Afrique.
Bull World Health Organ

1963
;
28(Suppl.)
:
1
–114.
Google Scholar
2
Moore PS. Meningococcal meningitis in sub-Saharan Africa: a model for the
epidemic process.
Clin Infect Dis

1992
;
14
:
515
–25.
Google Scholar
3
World Health Organization. Control of Epidemic Meningococcal Disease —WHO
Practical Guidelines. Lyon: Ed. Fondation Marcel Mérieux, 1995.
Google Scholar
4
Moore PS, Plikaytis BD, Bolan GA et al. Detection of meningitis epidemics in Africa:
a population-based analysis.
Int J Epidemiol

1992
;
21
:
155
–62.
Google Scholar
5
Varaine F, Caugant DA, Riou J-Y et al. Meningitis outbreaks and vaccination
strategy.
Trans R Soc Trop Med Hyg

1997
;
91
:
3
–7.
Google Scholar
6
Veeken H, Ritmeijer K, Hausman B. Priority during a meningitis epidemic:
vaccination or treatment?
Bull World Health Organ

1998
;
76
:
135
–41.
Google Scholar
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
:
30
–33.
Google Scholar
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
:
384
–90.
Google Scholar
9
WHO. Meningitis in the WHO African Region—Update, January-April 1997.
Wkly Epidemiol Rec

1997
;
72
:
131
.
Google Scholar
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.
Google Scholar
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
:
359
–64.
Google Scholar
12
Hassan-King MKA, Wall RA, Greenwood BM. Meningococcal carriage,
meningococcal disease and vaccination.
J Infect

1988
;
16
:
55
–59.
Google Scholar
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
:
114
–18.
Google Scholar
14
Kaninda AV, Varaine F, Henkens M, Paquet C. Meningococcal vaccine in sub-
Saharan Africa [comment].
Lancet

1997
;
350
:
1708
.
Google Scholar
15
Perkins BA, Broome C, Rosenstein NE, Schuchat A, Reingold AL. Meningococcal
vaccine in sub-Saharan Africa [comment].
Lancet

1997
;
350
:
1708
.
Google Scholar
16
Wenger J, Tikhomirov E, Barakamfitiye D, Bele O, Heymann DL. Meningococcal
vaccine in sub-Saharan Africa [comment].
Lancet

1997
;
350
:
1709
.
Google Scholar
17
Robbins JB, Towne DW, Gotschlich EC, Schneerson R. ‘Love’s labours lost’: failure
to implement mass vaccination against group A meningococcal meningitis in sub-
Saharan Africa.
Lancet

1997
;
350
:
880
–82.
Google Scholar
18
Lewis R, Varaine F, Belanger F, Nathan N, Diarra L. Control of meningococcal
disease in West Africa (Letter).
Lancet

2000
;
355
:
1185
–86.
Google Scholar
19
Consensus meeting on epidemic thresholds for meningococcal meningitis in
Africa. Wkly Epidemiol Rec 2000;(In Press).
Google Scholar
© International Epidemiological Association 2000
 Survival and sequelae of meningococcal
meningitis in Ghana
Abraham Hodgson Thomas Smith Sebastien Gagneux Isaac Akumah Martin AdjuikGerd Pluschke Fred
Binka Blaise Genton

International Journal of Epidemiology, Volume 30, Issue 6, 1 December 2001, Pages 1440–
1446, https://doi.org/10.1093/ije/30.6.1440

Published:

01 December 2001

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Abstract
Background Meningococcal meningitis epidemics are frequent in the Sahel zone of Africa but there
is little information on the frequency of long-term sequelae. We analysed excess mortality in the two
years following the 1997 epidemic in northern Ghana and carried out a case-control study to assess
sequelae in the survivors.
Methods Two-year survival of 696 meningitis cases recorded at the War Memorial Hospital,
Navrongo, was analysed using data from a demographic surveillance system. A structured
questionnaire on disability and on psychiatric, neuropsychological and behavioural problems was
administered to 505 of the survivors and 505 age- sex- and location-matched controls as well as to
their respective relatives. Cases and controls underwent full neurological and neuropsychological
examination and were evaluated for hearing impairment by audiometry.
Results Survival rates after the first month following the attack were similar in cases and controls.
Hearing impairment was the major sequela, and was reported in 6 per cent of cases and 2 per cent of
controls (odds ratio [OR] = 3.10; 95% CI : 1.48–7.09). Audiometry detected severe and profound
hearing loss in the worse affected ear (≥70 db) in 8/496 (1.6%) survivors but in only one control.
Survivors of meningitis were more likely to suffer from feelings of tiredness (OR = 1.47; 95% CI :
1.03–2.11) and were more often reported by relatives to have insomnia (OR = 2.31; 95% CI : 1.17–
4.82) and daily alcohol consumption.
Interpretation Meningococcal meningitis annually causes approximately 10 000 cases of deafness
in sub-Saharan Africa; there is a need for early detection of affected survivors and promotion of
simple hearing devices. There is a sizeable burden of depressive disorders secondary to meningitis
which should be identified and looked after appropriately.
Sequelae, mortality, survival, meningitis, Neisseria meningitidis, deafness, epidemic, Ghana

Issue Section:

INFECTIOUS DISEASES

Bacterial meningitis remains an important cause of morbidity and mortality, with the main
aetological agents outside the neonatal period being Streptococcus pneumoniae, Haemophilus
influenzae and Neisseria meningitidis. N. meningitidis meningitis is of major importance in the
meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8–12 years. For
example, in the 1996 epidemic in Burkina Faso, there were 42 129 cases with a case fatality rate
(CFR) of 10 per cent; in 1997 in Ghana, there were 18 551 cases, of whom 8 per cent died.1 The
World Health Organization (WHO) estimates that globally, there are 500 000 cases of
meningococcal meningitis each year with a CFR of 10 per cent. Of the cases, 250 000, and 27
000 of the deaths occur in the African region.1

Studies on survivors of bacterial meningitis have shown a wide range of neurological and
audiological2–11 as well as intellectual and behavioural sequelae.7,9,10S. pneumoniae has the highest
rates of sequelae4,12–15 as well as the highest case fatality.11–13

Many of the studies done specifically on meningococcal meningitis have been in developed
countries.16–18 In Africa, there have been very few studies on the sequelae of meningococcal
disease and fewer still on the survivors of epidemics,8,19 thus it is difficult to determine the
magnitude of the social burden caused by these epidemics. Despite high background levels of
disability in affected communities, there has been only one sequelae study that included
controls.8 In uncontrolled studies it is not possible to attribute the disability observed to the
meningitis per se.

There was a meningitis epidemic in the Kassena-Nankana district of Northern Ghana in 1997 in
which 1396 cases with 65 deaths were recorded at the district hospital and three health
centres.20 As is typical of epidemics in the belt, where major epidemics usually last for two or
three dry seasons dying out during the intervening rainy seasons,21,22 there was a resurgence of
the epidemic the next dry season; bacteriological analysis of samples from this resurgence
indicated that the causal organism was N. meningitidis serogroup A subgroup III;23 the
predominant organism of meningococcal epidemics in Africa during the 1990s. We now report a
case-control study of excess mortality, and neurological, psychiatric and neuropsychological
impairment amongst survivors of the 1997 epidemic. The goal was to assess the social burden
caused by the disease in Africa and to make recommendations for rehabilitation of survivors and
prevention of further disability.
Methodology

Study area
The Kassena-Nankana district (KND) is within the guinea Savannah area of northern Ghana
bordering Burkina Faso. It covers an area of 1675 sq km with a population of about 140 000. The
entire population of the district are included in a demographic surveillance system, the Navrongo
Demographic Surveillance System (NDSS), in which births, deaths, in and out migrations and
other demographic parameters are recorded in a database and updated every 90 days.24 Informed
consent was obtained from chiefs and elders in the area before the study began.

Survival study
A list of all clinically/laboratory diagnosed meningitis cases at the district hospital during the
1997 epidemic was compiled from the hospital records. In accordance with WHO guidelines, a
case was defined by sudden onset of fever and stiff neck, or fever and stiff neck and altered
mental status. Cases were traced during mid-1999 to ascertain or confirm their identification
numbers in the NDSS database and their vital status. All the patients identified were included in
the analysis of survival, and for each of them two controls, matched for age (±10%) and sex,
were also selected from the NDSS dataset of the population existing at the time of the epidemic.
A geographical information system was used to locate the nearest eligible controls to the home
of the case.

The NDSS was used to determine dates of death or migrations of both patients and controls.

Kaplan-Meier estimates of the survival curve were constructed separately for the patients and
controls for the period up to the end of June 1999. Migrating out of the district during that period
was treated as a censoring event.

Disability study
A simple random sample of the survivors of the epidemic who could be traced was included in
the disability investigation. For each of these cases, a list of possible controls aged within 10 per
cent of the age of the case and of the same sex as the case was generated from the NDSS dataset.
They were ordered by their proximity to the compound of the case using a geographical
information system. They were traced according to their order on the list; the chosen control
being the person living nearest to the home of the case, who had not suffered meningitis and who
was alive in mid-1999.

After informed consent had been obtained from both case and control and their relatives, an
appointment was made with them and both were transported to the hospital on the appointed day
with their relatives for investigation.

A trained research assistant who was blind to the case/control status administered a standard
questionnaire to cases, controls and their relatives. The questionnaire was adapted from a
previous one used in a national survey on disability,25 translated from English into the two local
languages (and back translated) then pre-tested among survivors of the 1998 outbreak, and
modified accordingly. It comprised separate sections for the subjects and for their relatives. In
the subject section, there was an open-ended question to those aged ≥6 years about the general
condition of their health over the past 2 years. Subjects and/or their relatives then answered a
series of closed questions to determine if the respondents had any major disability (Table 1) and
whether they were able to exercise daily living skills (feeding, cleansing, use of latrines,
dressing, understanding simple instructions, expression of needs, speaking and movement in the
home and community).

Subjects over 6 years old were then interviewed for symptoms of depression, anxiety, addiction
and psychosis (Table 2). Depressive and anxiety symptoms were graded either as (1) occurring
never or very rarely, (2) occurring sometimes, (3) occurring everyday. Possible addiction was
assessed by asking about the subject' alcohol intake, and was graded as whether he/she (1) never
took it or took it rarely, (2) took it sometimes, (3) took it daily. Psychotic symptoms were
categorized as either present or absent. To assess neuro-psychological status, subjects above 6
years were also asked a series of questions to assess their orientation in time, place and sense of
self. Memory was assessed by asking subjects to repeat the names of four items mentioned to
them, to reverse the order of the names of four animals mentioned to them, to recall the names of
these animals after an interval of about 15 minutes, and to remember what they had for breakfast
the previous day. General knowledge was tested by asking the names of the chief of the locality,
the head of state, and of the nearest big town. Those above 10 years were also asked to name the
first head of state of Ghana, to explain a local proverb, and to carry out simple mathematical
operations. These questions were adapted from questions generally used in medical practice to
examine the mental status of patients.26 Subjects who were deaf and dumb were not included in
this section of the interview.

Relatives were interviewed in the absence of the subject to ascertain the presence of disabilities
in subjects, to probe deeper into their psychiatric history, and to determine the severity of
detected symptoms. This also afforded the opportunity to see how well the answers given by
subjects correlated with those of the relatives. The relatives were asked whether they had noticed
any changes in the general health status of the subject, and invited to grade any difficulties
encountered by the subjects when compared to people of the same age. The relatives were also
asked about presence of depression, anxiety, addiction, and psychotic symptoms in the subject
(Table 3), and the playing habits of subjects less than 15 years old, the schooling of subjects aged
6–18 years, and the occupation of subjects more than 10 years old.

During questionnaire administration, sensitive issues were explored only after a good
relationship had been established. Confidentiality of the data obtained was assured.

After completion of the interview each subject underwent a neurological examination by a

physician who was blind to the case/control status, and who tested for cranial nerve palsies,
motor defects, cerebellar disorders and hydrocephalus. A Snellen chart placed at 6 m from the
subject was used to test for visual impairment. Pure tone audiometry using a portable screening
audiometer (Micromate, Denmark) was done after otoscopic examination for subjects ≥5 years.
Children under 5 years were tested by behavioural observation audiometry. Thresholds were
determined at 500, 1000 and 2000 Hz and hearing loss was classified as described by Dodge et
al.27

Completed forms were checked for completeness and internal consistency. Data were coded and
double entered into a computer using FoxPro. Matched analysis was done using standard Mantel-
Haenszel methods.

Results
Tracing
In all, 1077 admissions were recorded during the epidemic. Of these, 100 proved to be re-
admissions of the same individuals, leaving a total of 977 distinct patients. A total of 792 (81%)
of the 977 patients could be traced (Table 4). Sixteen of the people found denied that they had
suffered from meningitis, and so they could have been misidentified.

Survival study
Identification numbers within the NDSS could be determined for 696 patients. A total of 44 of
them (6.3%) and 15/1392 (1.1%) of the controls included in the survival analysis, died before
June 1999. The deaths among these patients were predominantly during the period of the
epidemic (Figure 1), with only 11 deaths more than one month after the admission date, and
eight deaths more than 2 months after admission. In the controls there were no deaths within 2
months of the admission of the matched case, but the death rate subsequently was very similar to
that of the cases, with a total of 15 deaths over the whole period. Log rank tests indicated that the
difference in survival over the whole period was highly significant (χ12 = 47.5, P < 0.0001) but
there was no significant difference in survival once the first month after admission was excluded.

Disability study
Overall, 505 meningitis survivors were investigated for disabilities, along with their matched
controls. The mean age for cases was 24.2 years (SD 15.4; range 2–73 years) and for controls
24.2 years, (SD 15.4, range 2–74 years). Thirteen (2.6%) of the cases were <5 years, 65 (12.9%)
were 5–9 years, 174 (34.5%) were 10–19 years, 80 (15.8%) were 20–29 years, 85 (16.8%) were
30–39 years, 47 (9.3%) were 40–49 years, 29 (5.7%) were 50–59 years and 12 (2.4%) were ≥60
years. The age distribution of the controls was not significantly different from that of the cases.
In each group there were 225 males and 280 females.

Disability

Fifty-four per cent of cases and 47 per cent of controls reported a change in the general condition
of their health over the past 2 years (Mantel Haenszel odds ratio [OR] = 1.46; 95% CI : 1.09–
1.96) indicating that meningococcal meningitis was indeed associated with subsequent
perception of ill health. Of the cases, 86/505 (17%), and 67/505 (13%) of the controls or their
relatives mentioned at least one disability (OR = 1.53; 95% CI : 0.99–2.39) (Table 1). The only
significant difference in the individual disabilities between cases and controls was in perceived
hearing impairment which was found in 6 per cent of cases and 2 per cent of controls (OR =
3.10; 95% CI : 1.48–7.09). There were no statistically significant differences between cases and
controls for other disabilities (Table 1). The only subject, a case, who was taking anti-
convulsants, reported a fit within the past year despite the medication.

Performance of daily living skills

There was no significant difference between cases and controls in their ability to perform daily
living skills, but the meningitis survivors tended to have more difficulties than controls. Ten per
cent of cases versus 8 per cent of controls mentioned one or more limitations of function. Three
cases were reported as not being able to keep themselves clean at all; one case was reported as
not being able to understand simple instructions at all and two cases could not speak at all. Apart
from a prevalence of 9 per cent in cases and 7 per cent in controls in inability to clean self, no
other disabilities occurred in more than 3 per cent of either group.

Psychiatric and neuropsychological status

Prevalence of depressive, anxiety and psychotic symptoms are presented in Table 2. Five cases
and two controls reported daily aches and pains; three cases reported daily tiredness. Survivors
of meningitis were more likely to suffer from feelings of tiredness or having little energy (OR =
1.47; 95% CI : 1.03–2.11). There was no other significant difference. A score was constructed by
assigning 0 if the subject reported no or very occasional depressive or anxiety symptoms, 1 if
he/she reported them to occur sometimes and 2 if he/she reported them to occur every day. The
mean of this score was 1.77 for cases and 1.66 for controls. This difference was not statistically
significant. Only four cases and three controls mentioned a daily intake of alcohol. There were
no significant differences between cases and controls in their ability to answer the questions in
the neuropsychological questionnaire.
Relative interview

In 152/505 (30%) instances relatives of cases had noticed a change in the health status of their
relation, as compared to 112/505 (22%) of the families of the controls (OR = 1.70; 95% CI :
1.21–2.4). The finding is similar to rates reported by the patients themselves.

Cases seemed to be more involved in social activities than controls. Some 0.4 per cent of cases
versus 2 per cent of con- trols were not participating in family activities and 4 per cent versus 7
per cent in community activities (OR = 0.38; 95% CI : 0.15–0.90). There was no significant
difference between responses of relatives of cases and controls to the question about whether
subjects had any difficulty. However in 8/16 cases the difficulties faced by the case were rated as
severe by the relatives, as compared to 0/12 of the controls.

The prevalence of anxiety, depressive and psychotic symptoms reported by the relatives is shown
in Table 3. The relatives claimed that cases tended to have more sleep difficulties than controls.
With this exception the differences were not statistically significant, but in general, a greater
proportion of cases than controls tended to have depressive and anxiety symptoms. Eight
relatives of cases mentioned a daily alcohol intake versus one relative of a control (P = 0.02).
One case shut himself up alone every day, one case had difficulty sleeping every day, one case
tended to worry every day and two cases and one control were easily annoyed every day.

For each subject, assigning a score of 0 if he/she never had a depressive or anxiety symptom or
had it very rarely, 1 if he/she had it sometimes and 2 if he/she had it every day, the mean score
for cases was 0.34, and for controls 0.23 (P = 0.14).

There was no significant difference between cases and controls in employment, playing habits,
or school attendance. Two per cent of 170 paediatric cases and 1 per cent of the corresponding
controls did not play like children of the same age; 28 per cent of the 213 cases of school age and
27 per cent of their controls were not attending school. However, among those attending school,
12 per cent of cases had problems versus 6 per cent of controls (OR = 2.40; 95% CI : 0.79–8.70).
Seventeen per cent of cases and 16 per cent of controls had repeated the previous year in school.
Among adults, 264/280 (94%) cases as compared to 258/282 (92%) controls had inadequate
income for their needs.
Clinical examination

All 505 cases and 505 controls were examined. Only one subject, a 6 year old case, was ill-
looking. He had a history of convulsions and an extensive ulcer on the forehead due to repeated
falls during attacks. There were no cases of hydrocephalus. One case had tremor which was
associated with alcohol consumption.

The frequencies of cranial nerve abnormalities ranged from 0 per cent for nerves V, VII, XI, or
XII to 13 per cent for nerve I. There was no significant difference between cases and controls,
except for an excess of hearing problems in cases: severe and profound loss in the worst affected
ear (≥70 db) in 8/496 (1.6%) of cases versus 1/495 (0.2%) of controls (OR = 8.0; 95% CI : 1.07–
355). Of those in whom hearing loss was detected, 8/32 (25%) of cases and 1/21 (4.8%) of
controls had a severe or profound loss (Table 5).

There was a tendency for cases to have more hyperreflexia than controls; the difference was
significant in the upper limbs (78/505 [15%] versus 55/505 [11%]; OR = 1.56; 95% CI : 1.04–
2.37). All 1010 subjects had normal plantar reflexes.

All cases and controls had normal bulk and tone for all four limbs, as well as normal power in
the upper limbs except for one case who had grade 4 power in the left upper limb, and another
who had grade 3 power in the right upper limb. Only one case and two controls had power <5 in
one of the lower limbs.

Discussion

The survival analysis showed that 94 per cent of the meningococcal meningitis cases that
reported to the hospital survived the epidemic. After the acute phase, the death rate was very
similar to that of the controls. These findings contrast sharply with the known outcome of
meningitis caused by Streptococcus pneumoniae or Haemophilus influenzae which lead to much
higher immediate case fatality rates and significantly higher long-term mortality.11Besides the
potential difference in virulence of the micro-organism, it is likely that the age at which the
meningitis occurs plays a role. Meningoccal meningitis occurs in older individuals, especially
during epidemics, and they are likely to have a better ability to fight the disease, and hence its
complications. Since the mortality attributable to meningoccal meningitis is mainly related to the
acute episode, there is a need to focus the efforts on this phase in order to reduce the number of
deaths, and probably also the incidence of sequelae. The community should be well aware of the
forthcoming epidemic and of the importance of seeking medical care early in the course of the
disease.

The survivors of meningitis were more likely to suffer ill-health than controls. The most
dramatic impairment was in hearing loss where 1.6 per cent of cases and 0.2 per cent of controls
had severe or profound hearing loss which confirms previous reports.8,19 The excess risk of self-
reported hearing impairment among the cases was 4 per cent, which implies that in Africa, where
there are about 250 000 cases of meningococcal meningitis each year,1the disease leaves
approximately 10 000 people in the region with impaired hearing. Besides treating acute
episodes early, there is a need to improve the detection of cases with hearing impairment and to
promote the distribution of simple hearing devices in communities where meningitis epidemics
occur.

There was a general tendency for cases or their relatives to report disabilities or reduced
performance of daily living skills more often than controls. All subjects with severe limitation of
function (not being able to perform the skill at all) were meningitis cases, and although these
form only one per cent of meningitis cases this is of importance since these people will need full
support for their entire life. The use of more advanced tests for mental retardation and
behavioural problems, which are difficult to apply in this setting, may have picked up more
differences between the two groups.

There has been no attempt in the past to assess the incidence of psychiatric disorders attributable
to an episode of meningococcal meningitis. We found that meningitis survivors reported more
often feeling tired or having little energy than controls. Relatives mentioned also more sleeping
difficulties and increased alcohol consumption for cases. The latter item was significantly
different only from the relatives' perspective, which is expected for health problems associated
with community stigma. There may have been some bias in reports of ill health following the
meningitis episode since meningitis cases and their relatives were sensitized to the possibility of
illness following the meningitis episode. However, in general, the fact that the relatives
independently gave similar answers to those of the subjects provides some internal validation for
the responses. Our findings suggest that an episode of meningitis can favour the occurrence of
depressive symptoms and hence alcohol addiction. Since our psychiatric assessment was rather
rudimentary, we may well have underestimated the true incidence of depressive illness
secondary to meningitis. This problem can pose a substantial burden for the family and society in
general. The challenge is to be able to identify the meningitis survivors who are affected, and to
offer them decent specialized care.

Interestingly, the social integration of the survivors did not appear to have suffered, and indeed
there may have been an increase in social activity, possibly because of reduced social pressure to
engage in physical work. There was no relationship between having had meningitis in the past
and employment or adequacy of income. This may be due to the general poverty in the area
where almost everyone is engaged in subsistence farming. However, with increasing
urbanization, social integration of survivors may become more of a problem.

We found no evidence of neuropsychological sequelae. It may well be that the assessment was
not sensitive enough to detect small differences in memory, orientation, abstraction etc., although
the questionnaire was based on validated instruments used in other developing countries.

The percentages of cases and controls attending school were similar, but in the cultural setting of
Northern Ghana, the decision to send a child to school depends less on intellectual performance
than on fee-paying ability and the demands of domestic and farming activities. However, cases
tended to report more learning problems at school than controls.

Meningococcal meningitis has a lower case fatality rate than meningitis caused by other
bacteria like Streptococcus pneumoniae.13 The incidence of long-term sequelae, which in this
study were mainly hearing impairment and depressive disorders, is also lower than that
following Streptococcus pneumoniae, Haemophilus influenzae11,13 or Escherichia coli meningitis.
However, most of the previous studies did not include controls from the general population in
their assessment, so the mortality rate and the incidence of sequelae may have been largely
overestimated in the past, especially in unprivileged populations where other diseases such as
cerebral malaria and otitis media lead to the same type of health problems. Even if the fraction of
sequelae attributable to meningococcal meningitis is lower than expected, it still poses a sizeable
 burden of disease in communities where repeated epidemics occur involving up to 5 per cent of
the population. The sequelae need to be recognized and looked after appropriately.

KEY MESSAGES

 There is little information on the long-term survival and frequency of sequelae from
meningococcal meningitis because of the difficulties in adequately tracing cases and precisely
evaluating the meningitis-specific disabilities in populations where several diseases can be
responsible for the observed pathologies.
 Excess deaths occurred during the first 30 days after the onset of meningitis; survival rates after
the first month were similar in cases and controls.
 Hearing impairment was the major sequela, and was reported in 6 per cent of cases and 2 per
cent of controls. Survivors of meningitis were more likely to suffer from symptoms of depression
and were more often reported by relatives to drink alcohol daily.
 Meningococcal meningitis is one of the important cause of deafness in sub-Saharan Africa ; there
is a need for early detection of affected survivors and promotion of simple hearing devices.
There is a sizeable burden of depressive disorders secondary to meningitis which should be
identified and cared for appropriately.
Table 1

Disability
Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

a Odds ratio.

Responses were obtained for all 505 cases and 505 controls.

Difficulty in moving any part 0.89 (0.42–

of body 22 (4.4) 24 (4.8) 0.03 1.85) 0.86
 Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

1.00 (0.56–
Difficulty in seeing 42 (8.3) 42 (8.3) 0.02 1.79) 0.89

Difficulty in hearing normal 3.10 (1.48–

speech 31 (6.1) 10 (2.0) 9.8 7.09) 0.002

Loss of feeling in hands or

feet 1 (0.2) 0 (0.0) 0.0 – 1.00

Difficulty in speaking like 2.33 (0.53–

person of same age 7 (1.4) 3 (0.6) 0.9 14.0) 0.34

Episodes of fits in the last 1.00 (0.07–

year 2 (0.4) 2 (0.4) 0.3 13.8) 0.62

86 1.53 (0.99–
Any of the above disabilities (17.0) 67 (13.3) 3.6 2.39) 0.059

View Large

Table 2

Self-reported psychiatric symptoms

Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

a Odds ratio.

Responses were obtained for 469 cases and 471 controls.

 Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

Depressive and anxiety

symptoms

384 0.96 (0.63–

Aches and pains (81.9) 388 (82.4) 0.01 1.46) 0.92

Tiredness or having little 188 1.47 (1.03–

energy (40.1) 163 (34.6) 4.60 2.11) 0.03

1.35 (0.79–
Difficulty in sleeping 41 (8.7) 32 (6.8) 1.05 2.33) 0.31

0.92 (0.37–
Tendency to cry 13 (2.8) 14 (3.0) 0.00 2.27) 1.00

1.10 (0.42–
Suicidal tendencies 11 (2.3) 10 (2.1) 0.00 2.89) 1.00

0.88 (0.55–
Tendency to worry a lot 70 (14.9) 75 (15.9) 0.21 1.41) 0.65

1.05 (0.67–
Easily annoyed or irritable 65 (13.9) 63 (13.4) 0.01 1.64) 0.91

Episodes of great fear or 1.59 (0.96–

panic 51 (10.9) 36 (7.6) 3.21 2.68) 0.07
 Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

Any one of the above 410 1.09 (0.67–

symptoms (87.4) 410 (87.0) 0.05 1.77) 0.81

Psychotic symptoms

1.00 (0.13–
Auditory hallucinations 3 (0.6) 3 (0.6) 0.17 7.47) 0.68

1.00 (0.01–
Visual hallucinations 1 (0.2) 1 (0.2) 0.50 78.50) 0.48

1.67 (0.32–
Persecutory delusions 5 (1.1) 3 (0.6) 0.13 10.73) 0.72

View Large

Table 3

Psychiatric symptoms reported by relatives

Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

a Odds ratio.

Responses were obtained for all 505 cases and 505 controls.

Depressive and anxiety

symptoms
 Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

2.00 (0.29–
Shuts himself up alone 5 (1.0) 3 (0.6) 0.17 22.11) 0.68

2.31 (1.17–
Difficulty in sleeping 35 (6.9) 18 (3.6) 5.95 4.82) 0.01

1.71 (0.62–
Tendency to cry 13 (2.6) 8 (1.6) 0.84 5.14) 0.36

2.00 (0.43–
Suicidal tendencies 6 (1.2) 3 (0.6) 0.44 12.36) 0.50

1.55 (0.88–
Tend to worry 48 (9.5) 36 (7.1) 2.16 2.77) 0.14

1.36 (0.85–
Easily annoyed or irritable 61 (12.1) 49 (9.7) 1.55 2.21) 0.21

Any one of the above 1.35 (0.89–

symptoms 95 (18.8) 80 (15.8) 1.94 2.05) 0.16

Psychotic symptoms

2.50 (0.41–
Strange behaviour 6 (1.2) 3 (0.6) 0.57 26.25) 0.45

Auditory hallucinations 2 (0.4) 0 (0.0) 0.50 – 0.48

 Case n Controls n ORa (95% P-
(%) (%) χ 2 CI) value

1.50 (0.17–
Visual hallucinations 3 (0.6) 2 (0.4) 0.00 17.96) 1.00

0.80 (0.16–
Persecutory delusions 4 (0.8) 5 (1.0) 0.00 3.72) 1.00

1.00 (0.01–
Hurt self 1 (0.2) 1 (0.2) 0.50 78.50) 0.48

0.67 (0.06–
Refusal of food 2 (0.4) 3 (0.6) 0.00 5.82) 1.00

0.80 (0.16–
Unprovoked fighting 4 (0.8) 5 (1.0) 0.00 3.72) 1.00

View Large

Table 4

Results of tracing
n % of patients

Found alive (history of meningitis) 557 57.0

Found alive (no history of meningitis) 16 1.6

Dead 69 7.1
 n % of patients

Absent 150 15.4

Could not be traced 185 18.9

Re-admissions 100

Total admissions followed-up 1077

View Large

Table 5

Hearing assessment
Hearing class Cases n (%) Controls n (%) Total

The frequencies quoted are for the worse affected ear.

19 subjects could not do the audiometry because they were generally too young to understand the
procedure. They could all however hear normal speech.

Normal hearing (<30 dB) 464 (93.5) 474 (95.8) 938

Mild loss (30–55 dB) 17 (3.4) 18 (3.6) 35

Moderate loss (55–70 dB) 7 (1.4) 2 (0.4) 9

Severe/profound loss (≥70 dB) 8 (1.6) 1 (0.2) 9

Hearing class Cases n (%) Controls n (%) Total

Total 496 495 991

View Large

Figure 1

View largeDownload slide

Kaplan-Meier survival curves

We would like firstly to acknowledge the willing participation of the subjects and their relatives.
Technical assistance was provided by Pierre Ngom, Elizabeth Awine, Dickson Abanimi,
Boniface Atosona and Genevieve Avogo. Nathan Mensah was responsible for data management,
Mitchell Weiss assisted with questionnaire design, Kwaku Enos assured the co-operation of the
health services while Marcel Tanner and Alex Nazzar ensured excellent institutional support.
The study was financed by the Meningitis Research Foundation, and had ethical approval from
the Ghana Ministry of Health.

References
1

Tikhomirov E, Santamaria M, Esteves K. Meningococcal disease: public health

burden and control.

World Health Statist Q

1997

50

:
170

–77.
Google Scholar

Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD. Seizures and other neurologic
sequelae of bacterial meningitis in children.

N Engl J Med

1990

323

1651

–57.
Google Scholar

Ford H, Wright J. Bacterial meningitis in Swaziland: an 18 month prospective study

of its impact.

J Epidemiol Community Health

1994

48

:
276

–80.
Google Scholar

Carroll KJ, Carroll C. A prospective investigation of the long-term auditory-

neurological sequelae associated with bacterial meningitis: a study from Vanuatu.

J Trop Med Hyg

1994

97

145

–50.
Google Scholar

Choo KE, Ariffin WA, Ahmad T, Lim WL, Gururaj AK. Pyogenic meningitis in
hospitalized children in Kelantan, Malaysia.

Ann Trop Paediatr

1990

10

:
89

–98.
Google Scholar

Zaki M, Daoud AS, ElSaleh Q, West PW. Childhood bacterial meningitis in Kuwait.

J Trop Med Hyg

1990

93

–11.
Google Scholar

Salih MA, Khaleefa OH, Bushara M et al. Long term sequelae of childhood acute
bacterial meningitis in a developing country. A study from the Sudan.

Scand J Infect Dis

1991

23

175
–82.
Google Scholar

Smith AW, Bradley AK, Wall RA et al. Sequelae of epidemic meningococcal

meningitis in Africa.

Trans R Soc Trop Med Hyg

1988

82

312

–20.
Google Scholar

D'Angio CT, Froehlke RG, Plank GA et al. Long-term outcome of Haemophilus

influenzae meningitis in Navajo Indian children.

Arch Pediatr Adolesc Med

1995

149

1001
–08.
Google Scholar

10

Grimwood K, Anderson VA, Bond L et al. Adverse outcomes of bacterial meningitis

in school-age survivors.

Pediatrics

1995

95

646

–56.
Google Scholar

11

Goetghebuer T, West TE, Wermenbol V et al. Outcome of meningitis caused

by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The
Gambia.

Trop Med Int Health

2000

207
–13.
Google Scholar

12

Daoud AS, al-Sheyyab M, Batchoun RG, Rawashdeh MO, Nussair MM, Pugh RN.
Bacterial meningitis: still a cause of high mortality and severe neurological morbidity
in childhood.

J Trop Pediatr

1995

41

308

–10.
Google Scholar

13

Baraff LJ, Lee SI, Schriger DL. Outcomes of bacterial meningitis in children: a meta-
analysis.

Pediatr Infect Dis J

1993

12

389
–94.
Google Scholar

14

Jadavji T, Biggar WD, Gold R, Prober CG. Sequelae of acute bacterial meningitis in
children treated for seven days.

Pediatrics

1986

78

21

–25.
Google Scholar

15

Shaltout AA, Auger LT, Awadallah NB et al. Morbidity and mortality of bacterial
meningitis in Arab children.

J Trop Med Hyg

1989

92

402
–06.
Google Scholar

16

Schildkamp RL, Lodder MC, Bijlmer HA, Dankert J, Scholten RJ. Clinical
manifestations and course of meningococcal disease in 562 patients.

Scand J Infect Dis

1996

28

47

–51.
Google Scholar

17

Naess A, Halstensen A, Nyland H et al. Sequelae one year after meningococcal

disease.

Acta Neurol Scand

1994

89

139
–42.
Google Scholar

18

Ellsworth J, Marks MI, Vose A. Meningococcal meningitis in children.

Can Med Assoc J

1979

120

155

–58.
Google Scholar

19

Salih MA, Ahmed HS, Osman KA et al. Clinical features and complications of
epidemic group A meningococcal disease in Sudanese children.

Ann Trop Paediatr

1990

10

231

–38.
Google Scholar

20

Enos K. Cerebrospinal Meningitis in Northern Ghana: The Experience of the War

Memorial Hospital, Navrongo. Ministry of Health, Ghana [Report], 1997.
Google Scholar

21

Greenwood BM, Bradley AK, Wall RA. Meningococcal disease and season in sub-
Saharan Africa.

Lancet

1985

ii

829

–30.
Google Scholar

22

Greenwood B. Meningococcal meningitis in Africa. Manson Lecture. Royal Society

of Tropical Medicine and Hygiene meeting at Manson House, London, 10 December
1998.

Trans R Soc Trop Med Hyg

1999

;
93

341

–53.
Google Scholar

23

Gagneux S, Hodgson A, Ehrhard I et al. Microheterogeneity of serogroup A

(subgroup III) Neisseria meningitidis during an outbreak in northern Ghana.

Trop Med Int Health

2000

280

–87.
Google Scholar

24

Binka FN, Kubaje A, Adjuik M et al. Impact of permethrin impregnated bednets on

child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial.

Trop Med Int Health

1996

;
1

147

–54.
Google Scholar

25

Ngom P, Debpuur C, Bawah AA et al Survey on Disability in Upper East Region,

Ghana. Navrongo Health Research Centre documentation note No. 40. 1999
(unpublished).
Google Scholar

26

Berkow R, Fletcher AJ (eds). The Merck Manual of Diagnosis and Therapy. Rahway,
NJ: Merck Research Laboratories, 1992.
Google Scholar

27

Dodge PR, Davis H, Feigin RD et al. Prospective evaluation of hearing impairment as

a sequela of acute bacterial meningitis.

N Engl J Med

1984

311

869

–74.
Google Scholar

© International Epidemiological Association 2001