Meningitis Epidemics caused by Neisseria meningitidis in serum groups W135 and A in Burkina Faso in 2002, 2003 and 2004

 Dr. Daogo S. Zombré, Dr. Sylvestre R. M. Tiendrébéogo, Dr Souleymane Sanou

Meningitis is one of the most serious public health issues, especially in countries belonging to the African meningitis belt 1. Epidemics are recurrent in sub-Saharan Africa. One of the most serious epidemics occurred in 1996 when the World Health Organization recorded 188,341 cases in countries belonging to the African meningitis belt, numbering 42,967 cases only in Burkina Faso 2. Such epidemics were essentially attributed to the bacterium Neisseria meningitidis in serum groups A and C. 3,4
Despite this, Neisseria meningitidis W135 caused the cases of meningitis, which occurred on an international scale with a percentage ranging from 1 to 8 5,6. Before 2000 it was generally believed that this serum group’s invasive potential was negligible and that it was the cause of isolated foci involving less than 10 cases. 7
Neisseria meningitidis W135 proved to be the cause of 41% of very evident cases of meningitis during the pilgrimage to Saudi Arabia in 2000, besides it was isolated in non-immune individuals in 16 countries of the world, in Europe, in the United States and in Asia. 8
At the close of the 2001 epidemi season 32 on 58 samples from 14 different health districts in Burkina Faso proved positive to Neisseria meningitidis: 8 of these were positive to the bacterium in serum group A and 12 to the bacterium in serum group W135. 9
Such serious results justified the definition of preparatory plans designed to provide an immunological response to the new 2002 epidemic and also to 2003 and 2004 epidemics.
One of the strategies envisaged concerned the early recognition of epidemics and the subsequent isolation of germs, which cause the said cases of meningitis, by enhancing surveillance in all the country’s health districts. The network in charge of notifying cases, sampling and conveying subarachnoid fluid samples was strengthened along with district laboratories and reference laboratories’ analysis potential.
Epidemic control was enabled by making drugs, which are essential to treat the diseases, available in public health facilities, besides managing reactive mass immunization campaigns based on the availability of vaccines and on the germs, which cause the epidemics.
This study is designed to explain the evolution of meningitis’ epidemiological situation during the period 2002 - 2004 in an emergency framework for serum group W135 considered as the germ, which caused the first epidemic throughout the country, besides strategies implemented to control meningitis epidemics in Burkina Faso.

Methodology
Epidemic Control Data.
A retrospective analysis was conducted on control data referred to 2002, 2003 and 2004.
The said data was taken from weekly reports sent by health facilities, from reference laboratories’ reports on meningitis and from reports on the implementation of epidemic control strategies.
Weekly reports contain overall data concerning cases and deaths, which can be attributed to diseases marked by an epidemic potential. These reports are systematically forwarded by health districts and regions committed to the epidemiological control implemented by the Administration to Fight Disease. The notice is sent by all the country’s health facilities as a Weekly Telegram/Official Letter (TLOH - TLUS). The data reaches the main centre within 48 hours at most from the moment the weekly reports are filled out and completed. Indicators are analysed considering the health district, thus enabling early recognition of an abnormal situation, its assessment, the extent of the phenomenon and the trend of response strategies.
National reference laboratories’ reports on meningitis and reports from laboratories appointed to recognise the germs involved in each district are collected in the same manner. Subarachnoid fluid samples taken from cases of suspected meningitis are preserved in transport media (isolated media) and sent first to district laboratories and then to reference laboratories. District laboratories must perform analyses numbering leukocyte count, Gram staining and latex agglutination. Reference laboratories instead handle bacterial culture and study germ sensitivity to antibiotics.
Reports on the implementation of response strategies to epidemics have enabled to analyse the impact of interventions on the epidemiological situation’s evolution. These strategies have been defined by the national committee for epidemic management in the framework of the operational plan to fight epidemics in the reference period 2001 - 2005 and in the context of yearly preparation plans to respond to epidemics. Main trends comprise free treatment for these cases during an epidemic with oily chloramphenicol as frontline treatment, the implementation of reactive mass immunization campaigns in the districts involved by the epidemic and the sensitisation of populations.
Population Data. Health district population estimates were based on the population census performed in 1996 by the National Institute for Statistics and Demography (NISD). Population data, which is yearly updated, was obtained by applying the national yearly increase rate, which is 2.3%.
Calculating Indicators. The cumulative incidence of suspicious cases notified by districts was assessed in a three-year period and based both on the weekly estimate and on the epidemic period.
The epidemic period stretches from the first week of January to the second consecutive week during which no district reports suspicious cases or epidemics. Generally this period stretches from January to May.
The weekly rate of aggression was based on the ratio between the number of suspicious cases and the district’s population. This rate is expressed as the number of cases every 100,000 inhabitants and it has enabled to define a series of thresholds in the various districts. Depending on this rate, a district is alerted when it notifies from 5 to 9 cases in a sample of 100,000 inhabitants in a week, while it is concerned by an epidemic when it notifies at least 10 cases every 100,000 inhabitants in a week.
The death rate is the ratio between the number of deaths and the number of cases notified during the same period.
Data Processing. Data analysis has been performed with the software Epi Info 3.2, Excel and Health Mapper 4.1.

Results
In the period between 2002 and 2004, TLOH reports received by health facilities denounced 29,526 cases of meningitis on the whole. 2002 recorded the highest number of notified cases, which were 14,455 cases, while the two following years witnessed a reduced incidence of the disease. The mean death rate has settled at 15.2%.
The three reference years’ epidemic period stretches from January to May.
Figure 1 illustrates an increase in the number of cases starting from the fourth week of the year. Between 2002 and 2004 the epidemic’s peak moment occurred the second week of April (fourteenth week of the year), while in 2003 the peak moment appeared at an earlier date, late in February, during the eighth week. The epidemic’s peak moment was more serious in 2002.
The incidence of meningitis proved to be particularly serious during the 2002 epidemic period, while it recorded a regression in 2003 and 2004, as specified in Table 1. Considering the country’s 55 health districts, the epidemic occurred in 40% in 2002, in 21% in 2003 and in 11% in 2004.
This means that between 2002 and 2004 the incidence of meningitis and the number of districts undergoing an epidemic situation recorded a considerable reduction.
Results of bacterial identification conducted by reference laboratories reported in Table 1 reveal that the germ responsible for the epidemic was Neisseria meningitidis W135 in 2002.
The 2003 epidemic was instead a mixed epidemic of Neisseria meningitidis in serum groups A and W135 with a prevalence of serum group A.
The 2004 epidemic was instead essentially caused by Neisseria meningitidis A.
Between 2002 and 2004 the percentage of Neisseria meningitidis W135 recorded a reduction, while that of Streptococcus pneumoniae (Spn) and of Haemophilus influenzae B (HIB) increased.

Fig. 1
Curve comparative dei casi di meningite, Burkina Faso, 2002-2005
Courbes comparatives des cas de méningite, Burkina Faso, 2002-2005
Comparative plots of cases of meningitis, Burkina Faso, 2002-2005.

Discussion

Various epidemic foci have been found in Burkina Faso during the three consecutive years. Despite this intervals between epidemics in the African meningitis belt generally ranged between 5 and 10 years 10 in a context in which meningitis epidemics could essentially be attributed to Neisseria meningitidis A. The emergence of Neisseria meningitidis W135 as the cause of the 2002 epidemic could be behind the epidemic’s persistence during the following years in the measure in which populations lacked an immune defence against the said serum group. The serum group’s contribution however dropped during the following years.
Reasons for the emergence of W135 in Burkina Faso are still not clear. In fact no links have been noticed with the pilgrimage to Saudi Arabia. 11
Some theories, which attempt to explain the emergence of Nm W135, have been brought forward. It could be a new emergence of an old clone of the serum group W135, which was already isolated in Africa in the ‘90s 11,12 or a said genetic mutation of a clone of Neisseria meningitidis C towards the serum group W135. 14
Immune pressure exercised against serum groups A and C probably encouraged the emergence of a clone with a W135 polysaccharide. We recommend considering that the bivalent vaccine A+C is generally used to conduct preventive vaccination campaigns and to control epidemics in Africa.
Serum group W135’s percentage recorded a reduction in 2003 and in 2004. These years witnessed mixed epidemics with a prevalence of serum group A. One of the two serum groups has always proved to prevail on the other in epidemic districts, hence the competition between the two serum groups.
The percentage of Streptococcus pneumoniae and of Haemophilus influenzae B is increasing due to the reduced number of districts, which experienced an epidemic situation between 2002 and 2004. These bacteria generally cause cases of meningitis in non-epidemic districts. The percentage of these germs drops considerably in epidemic districts though their respective contribution during the epidemic period requires more accurate management and documentation.

 

Incidenza
Incidence
Incidence

Numero di distretti epidemici
Nombre de districts épidémiques
Number of epidemic districts

Germi identificati (% dei positivi)
Germes identifiés (% des positifs)
Germs identified (positive %)

 

Nm A

NmW135

Spn

Hib B

Anno/Année/Year

 

2002

109

22

3(2,1)

128(88,9)

7(4,8)

3(2,1)

2003

62

12

264(51,7)

104(20,4)

103(20,1)

40(7,8)

2004

37

06

244(37,1)

108(16,4)

244(37,1)

61(9,4)

Tab. 1
Incidenza della meningite e dei germi identificati dai laboratori, Burkina 2002-2004.
Incidence de la méningite et germes identifiés par les laboratoires, Burkina 2002-2004.
Incidence of meningitis and of germs identified by laboratories, Burkina 2002-2004.

Cases divided by age revealed that individuals aged below 30 years have paid a high contribution to meningitis during the three reference years. These age groups have been touched in identical proportions during the three years. Such results highlight the relevance of the choice of a target population aged between 2 and 30 years in conducting vaccination campaigns against meningitis.
The epidemic plot for 2002 recorded a trend towards a quick serious increase. This progress was the natural consequence of the lack of vaccines against Neisseria meningitidis W135, the cause of the epidemic, and the impossibility to effectively immunise the population. In fact the tetravalent vaccine A+C+Y+W135 was not available in an adequate quantity and the cost was absolutely prohibitive. This situation led the World Health Organization to perfect limited quantities of a trivalent vaccine A+C+W135 at the close of 2002. This vaccine was first used on a large scale to control the epidemic, which occurred in Burkina Faso in 2003.
The main strategy for 2002 was implemented by strengthening disease management, by preventively concentrating drugs and consumption material in health facilities in all levels of the very National Health Service, in adjusting stocks of drugs and consumption materials to suit the epidemiological situation, besides supervising operators’ training concerning case management.
Information and the populations’ sensitisation have led to collective participation in epidemic control activities.
Epidemic management was ensured by the many levels of the National Health Service’s various coordination organs. The said organs were appointed to coordinate and mobilise the human resources required and to direct and manage control strategies.
Besides strategies implemented in 2003, the trivalent vaccine’s availability against germs A, C and W135 and the bivalent vaccine’s availability against A and C ensured an equal number of vaccination campaigns in the twelve epidemic health districts. These interventions led to a bend in the plot with a reduced incidence and an epidemic peak, which appeared at an earlier date and was less extensive than in 2002. This trend symbolised the trivalent vaccine’s efficacy, which would have probably caused a considerable drop in the number of cases within a maximum term of two weeks from the reactive vaccination’s administration in districts experiencing an epidemic situation.
Administrative data on vaccine coverage implemented proved to be over 85%.
The population’s Increased immunity against serum groups A and W135 explains the lesser incidence of meningitis in 2004 numbering only six epidemic districts. The vaccination performed in the first districts during an epidemic situation also contributed towards the 2004 epidemic’s reduced range of action.
Fig. 2
Ripartizione geografica dei distretti epidemici, Burkina Faso, 2002-2004.
Répartition géographique des districts épidémiques, Burkina Faso, 2002-2004.
Geographical division of epidemic districts, Burkina Faso, 2002-2004.

Conclusion

In 2002 the emergence of Neisseria meningitidis W135 altered the epidemiological pattern of meningitis in Burkina Faso. From 2002 onwards the country witnessed mixed epidemics marked by a gradual return of serum group A. The correct management of these serum groups should hence be strengthened to ensure better epidemic prevention.
The implementation of effective strategies in the operational plan’s framework and the response to epidemics ensure more effective epidemic control.
The best way to fight meningitis epidemics caused by meningococci in Africa lies in perfecting a combined vaccine, which, inserted in the extensive vaccination programme, would enable to conduct preventive and supplementary mass vaccination campaigns.
  Cloramfenicolo oleoso
Chloramphénicol huileux
Oily chloramphenicol
Ampicillina
Ampicilline
Ampicillin
Vaccini (fiale)
Vaccins (doses)
Vaccines (phial)
Copertura vaccinale (%)
Couverture vaccinale (%)
Vaccine Coverage (%)
      A+C A+C+W135 average - deviation
Anno/Année/Year  
2002 131 890 50 450 0 0 -
2003 134 530 192 680 53 350 1 998 500 93,7 (88-101,9)
2004 42 200 80 900 280 360 130 000 106,0 (92-113,1)
Tab. 2
Farmaci e vaccini utilizzati per il controllo delle epidemie, Burkina Faso 2002- 2005.
Médicaments et vaccins utilisés pour le contrôle des épidémies, Burkina Faso 2002- 2005.
Drugs and vaccines used to control epidemics, Burkina Faso 2002- 2005.

Fig. 3
Ripartizione dei casi di meningite in funzione dell'età, Burkina Faso 2002-2004
Répartition des cas de méningite selon l'âge, Burkina Faso 2002-2004
Division of meningitis cases by age, Burkina Faso 2002-2004.


Acknowledgments

We wish to thank all the people acting in the National Health Service in health districts and regions, besides laboratory technicians. We appreciate the technical, logistic and financial support of health partners in Burkina Faso, who have contributed actively towards epidemic control. We wish to specially mention the WHO, the UNICEF, the Red Cross, the association Doctors without Borders, Pharmacists without Borders, bilateral cooperation projects (Italian, French, Dutch, Belgian, Canadian), the European Union and the WHO’s collaborating centres (CDC, Oslo).

Zombré DS
General Management, Department of Health, Ouagadougou, Burkina Faso
Tiendrébéogo SR, Sanou S Ouédraogo D, Dabal M
Administration to Fight Disease, the Ministry of Health, Ouagadougou, Burkina Faso
Ouédraogo RT
Charles de Gaulle Paediatric Hospital Laboratory, Ouagadougou, Burkina Faso
Sanou I
University Hospital Laboratory, Ouagadougou, Burkina Faso