Epidemic group C meningococcal meningitis in Upper Volta, 1979

Bulletin ofthe World Health Organization, 61(2): 325-330(1983) Epidemic group C meningococcal meningitis in Upper Volta, 1979 CLAIRE V. BROOME,1 MICHAEL A. RUGH,2 ADAMOU A. YADA,3 LEVAN GIAT,4 HIEN GIAT, JEAN MARIE ZELTNER,3 WARREN R. SANBORN,5 & DAVID W. FRASER' Group C meningococci were isolated during an epidemic ofmeningococcal meningitis which occurred between January and May 1979 in eastern Upper Volta, an area previously associated with endemic and epidemic groupA disease. A total of539 cases ofmeningitis, 55 of which were fatal, were reported, giving an attack rate of 517 cases per 100 000 inhabi- tants. Attack rates were higher for children under 15 years of age. Clinical and bacterio- logical data suggested that the group C meningococci were sulfonamide-resistant. The last meningococcal epidemic in Upper Volta occurred in 1970 and was nationwide. Epidemic cycles ofgroupA meningococcal meningitis have occurred at 10-1Syear intervals in thesub- Saharan region, raising concern that the current increase in activity maypresage more wide- spread disease in the next dry season. The "meningitis belt" of sub-Saharan Africa was initially characterized by Lapeyssonnie as an area of hyperendemic meningitis with periodic epidemic waves at 10-15-year intervals (1). Disease occurred almost exclusively during the dry season, from December to April. Although few bacteriological studies have been done, most suggest that the group A meningococcus has been the predominant pathogen, especially during epidemic waves (1). However, Whittle et al. (2), on the basis of counterimmuno- electrophoresis (CIE) and latex agglutination studies, reported that 71 of 133 cases in northern Nigeria in 1975 were caused by group C meningococci. They suggested the possibility that sulfonamide resistance, which is common in group C strains elsewhere, might also be present in this area where long-acting sulfona- mides have been used as therapy for meningitis. Investigating a localized outbreak of meningitis in eastern Upper Volta in 1979, nine years after the previous outbreak in that country, we isolated group C meningococci, which appeared to be sulfonamide- resistant. We also characterized the epidemiology of meningitis in the area, permitting some comparison with epidemic meningococcal disease in other areas. Bacterial Diseases Division, Center for Infectious Diseases, Centers for Disease Control, Atlanta, GA 30333, USA. 2 US Agency for International Development, Ouagadougou, Upper Volta. 3 Ministry of Public Health, Ouagadougou, Upper Volta. 4 World Health Organization, Ouagadougou, Upper Volta. s Naval Health Research Center, San Diego, CA, USA. METHODS Epidemiology A person was considered to have meningitis if the diagnosis had been made by government health personnel. Statistics on reported meningitis cases in previous years were obtained from the Ministry of Health, Ouagadougou, Upper Volta. Details of cases occurring in January-March 1979 were found by review of dispensary records for the period. Infor- mation on cases that occurred after that time is based on case reports to the Ministry of Health. Rates given for 1979 reflect the cases reported up to May of that year and have not been adjusted to an expected total for the entire year. Population data for Upper Volta are based on the 1975 estimates, adjusted on the assumption of a 2.3070 annual increase (3). Infor- mation on age distribution of cases in previous years was taken from the annual reports of the Ministry of Health. Age distribution of cases for the current season was based on a review of dispensary records at the time of the investigation. Laboratory methods Laboratory tests were not performed routinely on meningitis cases in Upper Volta. In some cases, patients underwent lumbar puncture to ascertain the opacity of the cerebrospinal fluid (CSF). CSF specimens obtained from cases diagnosed during the 4286 -325- C. V. BROOME ET AL. investigation were inoculated on cystine trypticase agar; subcultures were later made on Mueller-Hinton agar. CSF samples were also tested by counter- immunoelectrophoresis (CIE) (4); however, the lack of refrigeration facilities meant that all specimens were maintained at room temperature (maximum, 35-42 'C) for 30-35 days before this test. In the CIE, all specimens were tested with antisera against groups A, B, and C Neisseria meningitidis, polyvalent and type b Haemophilus influenzae, and polyvalent Streptococcus pneumoniae. Specimens that were negative for the above antigens were tested with anti- sera against groups D, 29E, W135, X, Y, and Z N. meningitidis, polyvalent Salmonella, and Strepto- coccus pyogenes. CIE was able to detect 0.1 tg of group A or C polysaccharide per ml and 0.5 Ag of group B polysaccharide per ml. Minimum inhibitory concentration (MIC) of sulfadiazine was determined for each isolate by agar dilution (5). RESULTS Upper Volta has had periodic epidemics of menin- gitis in the last 40 years, with peak numbers of cases occurring in 1945, 1957, and 1970 (Fig. 1). The number of cases has generally remained above base- line for 1-4 years after the peak year of an epidemic. During the epidemic of 1970 the incidence of reported cases varied widely by region from 250 cases per 100 000 to 925 cases per 100 000 (Fig. 2). It is also notable that in the year before the nationwide outbreak in 1970, several regions had an incidence above background level. During the 1979 meningitis season, the Eastern region (region II) had an incidence 4-5 times that of the country as a whole. Cases in this region occurred predominantly in the subprefecture of Diapaga, near the border with Niger. A total of 539 cases, 55 of them fatal, were reported from this subprefecture between 1 January and 31 May, 1979, giving an attack rate of 517 cases per 100 000 population. The age distribution of 407 of the cases in Diapaga with onset between 1 January'and 19 March 1979, found by review of dispensary records, is shown in Table 1. Over 80Wo of the cases were in persons under 20 years old. The highest attack rate, 810 cases per 100 000 population, occurred in children 1-4 years of age (Fig. 3). Review of dispensary records showed that the first cases were diagnosed in the dispensary at Diapaga, at the centre of the subprefecture. Two weeks later, cases were diagnosed in a dispensary in Namonou, a town 27 km south-west of Diapaga. Four weeks after the initial diagnosis, cases began to be diagnosed at Kantchari, 56 km north-west of Diapaga, on the main road to the capital. U, v) 10000 9000- 8000- 7000 6000 5000 4000- 3000 2 000 1000- 0 1940 '45 '50 '55 '60 '65 '70 '75 '80 Fig. 1. Annual number of cases of meningitis reported in Upper Volta, 1939-79 Treatment of meningitis was primarily by intra- muscular injection of a long-acting sulfonamide and/or chloramphenicol. Patients who were in coma when first seen for treatment received chloram- phenicol initially; those thought to have mild disease were given long-acting sulfonamides. A total of 55 patients died, and the date of death is known for 28. Of these, 16 died within 24 h of arriving at the dispen- sary, and 8 died on the second day after admission; thus 867o of deaths occurred within the first 48 h of the patient receiving medical attention. Analysis of dispensary records in Diapaga showed that in 81 cases initial therapy was with long-acting sulfonamides alone. Of these 81 patients, 73 survived at least 48 h after treatment; 3 subsequently died. In an additional 326 GROUP C MENINGOCOCCAL MENINGITIS IN UPPER VOLTA 000 900 800 5000 2000- 1000- 700 I - -|\- I I( NCLUDES DIAPAGA) zI o :VI 4 600 ALL SECTORS 0 400 2000 , 0 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 Fig. 2. Incidence of meningitis in various regions of Upper Volta, 1965-79. Sector is the central region; sector 11 is the eastern region; and sector IV is in the north of the country. The data have been corrected to allow for regional boundary changes in 1975. The figure for 1979 is for the first five months only. Table 1. Diapaga 1979 Age distribution of cases of meningitis in subprefecture, Upper Volta, January-March AttackCases rate Age (per 100 000 (years) No. % population) < 1 22 5.4 500 1-4 110 27.0 810 5-9 103 25.3 740 10-14 61 15.0 500 15-19 35 8.6 330 20-24 1 9 4.7 200 25-29 1 7 4.2 210 30-39 20 4.9 160 ,40 9 2.3 50 Unknown 11 2.6 Total 407 100.0 517 cr > (r cL0. 0 cr u) 327 DIAPAGA, 1979 --- UPPER VOLTA, EPIDEMIC YEAR, 1970 - -- SAO PAULO BRAZIL MENINGOCOCCAL MENINGITIS. EPIDEMIC YEAR, 1974 (10) .UPPER VOLTA, NON-EPIDEMIC YEARS, 1974-1975 --------- SPORADIC MENINGOCOCCAL MENINGITIS, UNITED STATES, 1970 (13) 5 10 15 20 25 30 35 40+ AGE (YEARS) Fig. 3. Age-specific incidence of meningitis in various populations. The data for Diapaga are for 1 January- 19 March 1979. 10 cases, chloramphenicol or penicillin was given on the third day of hospitalization, presumably because the patients did not respond to sulfonamides alone. Therefore, in 13 of 73 cases (1807o) there is evidence of a poor clinical response to sulfonamides, and a further 8 patients receiving sulfonamide alone died within 48 h of reaching the dispensary. Bacteriological results Of 18 CSF specimens tested by CIE, 8 were positive for serogroup C meningococci. In addition, sero- group C meningococci were isolated from 4 CSF specimens that had been positive by CIE. The tests for other pathogens were negative. The sulfadiazine MICs for the strains isolated were 40, 40, 64, and 128 Ag/ml, levels consistent with in vitro resistance. DISCUSSION Analysis of the epidemiological data from this and earlier outbreaks of meningitis in Upper Volta is C. V. BROOME ET AL. hampered by the absence of bacteriological data in the majority of cases. However, the clinical diagnosis of meningitis is probably valid in most cases, and the most likely causative agent of epidemic bacterial meningitis is the meningococcus. In such outbreaks, a particular strain probably predominates, so that even limited bacteriological test results may provide useful information and help improve our understanding of epidemic meningitis in this area. The bacteriological data from Diapaga are of considerable interest, as all the organisms identified by either culture or CIE were serogroup C. The few previous studies of the bacteriology of meningococcal disease in this area between 1934 and 1970 reported only group A disease (1). All 6 isolates received by the Centers for Disease Control (Atlanta, GA, USA) from Upper Volta during the 1970 outbreak were group A (P. Hayes, personal communication, 1979). However, Whittle et al. identified group C meningo- coccus by CIE and latex agglutination in northern Nigeria in 1975 (2). Our finding of group C strains, in association with epidemic disease, may indicate the need to consider group C meningococci as a possible cause of epidemic meningitis in this region. Only 44°0o of CSF specimens obtained in Diapaga were positive, although the sensitivity of CIE is usually around 70% (4, 6). This apparent decrease in sensitivity may be related to the conditions under which the CSF specimens were stored in the field. Outbreaks of group C meningococcal disease have been reported from Dade County, Florida, and Sao Paulo, Brazil (7, 8). However, the meningitis attack rate in Diapaga of 517 per 100 000 inhabitants per year was over 30 times greater than the attack rates in these other group C outbreaks. The attack rate in Dia- paga was similar to that seen in the Chilean group A outbreak in 1942 and the Brazilian group A outbreak in 1974-75 (9, 10). The occurrence of this localized outbreak 9 years after the previous countrywide epidemic raises con- cern that the disease may be more widespread in the next season. In the past, epidemics in Upper Volta have occurred at 12 or 13-year intervals (Fig. 1) and have sometimes been preceded by local outbreaks (Fig. 2). Hedrich, in the early 1900s, observed intervals of 6-12 years between epidemic peaks (11). However, it is not known whether the epidemiology of group C disease will parallel that of group A disease. Also of concern is the possibility of epidemic group A disease following epidemic group C disease as in Brazil (10) and Nigeria (12). It is important to continue epidemiological studies to examine these points; improved antigen detection methods for use in the field would facilitate the collection of important bacteriological data. The age-specific attack rates for meningitis in Diapaga and Upper Volta as a whole differ from those reported for other areas (Fig. 3). In both epi- demic and non-epidemic periods in Upper Volta, attack rates are similar for all age groups of children under 15 years and decline steadily thereafter with increasing age. The much higher attack rates for chil- dren under 1 year of age and the marked fall in incidence by age 10 years, seen in the 1974 Brazil epi- demic and in endemic cases in the United States of America, have not been noted in Upper Volta (10, 13). Lapeyssonnie, in his study of the "meningitis belt" in Africa, also noted that as many as 50%0 of patients were over 15 years of age, and approximately one-third were 5-15-year-olds. However, his data do not permit calculation of attack rates (1). The finding that all 4 group C strains isolated were sulfonamide-resistant, in conjunction with the apparently poor clinical response to sulfonamide therapy, has important implications for treatment of meningococcal disease. Sulfonamide resistance in group A meningococci has already been noted in Africa; Belcher et al. found that 7% of group A strains isolated from the CSF of patients in Ghana in 1975 were resistant to 10 tsg of sulfadiazine per ml (6). The current alternative therapy suggested is chlor- amphenicol, administered intramuscularly (14). In areas that have previously relied on a single injection of long-acting sulfonamides, the 4 injections of chlor- amphenicol required per day may not be feasible. An alternative recommendation that mobile teams give a single injection of chloramphenicol in oil suspension as therapy for meningitis has not yet been fully evaluated, although preliminary studies suggest that blood levels of 2-4 yg/ml can be obtained 36-48 h after injection of 0.05-0.1 g per kg of body weight (15, 16). Classification and documentation of the extent of sulfonamide resistance is needed to stimulate the development and implementation of alternative therapies. It seems likely that the currently available bivalent group A and C vaccine should be effective in control- ling any outbreak of meningitis, as it seems to have been in Brazil (10) and Finland (17). Since the disease tends to recur at levels above baseline for 1-4 years following an epidemic peak, administration of the vaccine to inhabitants of the regions involved should reduce the number of cases in subsequent meningitis seasons, although there is the suggestion from a field trial in Egypt that the duration of protection given by group A vaccine may be as short as 1 year (18). Whether the vaccine should be restricted to the sub- prefectures currently involved and their immediate surroundings or should be distributed throughout Upper Volta is not clear, but the issue is important since the resources necessary to immunize all inhabitants of Upper Volta would be considerable. A recent study by Greenwood suggests that the rapid immunization of inhabitants of villages where a case 328 GROUP C MENINGOCOCCAL MENINGITIS IN UPPER VOLTA 329 has been identified may prevent subsequent cases (19). However the logistics of implementing this strategy need further study. The government of Upper Volta has immunized the residents of Diapaga and surrounding areas. Epidemiological and bac- teriological surveillance during the next menin- gitis season should be used to evaluate the success of that strategy. ACKNOWLEDGMENTS We gratefully acknowledge the laboratory support of Ms Peggy S. Hayes, Dr Clyde Thornsberry, and Ms Linda K. McDougal of the Centers for Disease Control, Atlanta, GA, and of Dr Charles Saccharin and Dr Isaac Toure of the Centre Muraz, Organisation de Coordination et de Cooperation pour la Lutte contre les Grandes Endemies, Bobo Dioulasso, Upper Volta. Boubakary Amadou Tamboura and Parou Ouoba, Infirmiers d'Etat, assisted in gathering data and specimens in Diapaga. The United States Agency for International Development provided funds and logistical support for the investigation. RESUME MENINGITE EPIDEMIQUE A MENINGOCOQUES DU GROUPE C EN HAUTE-VOLTA, EN 1979 Des meningocoques du groupe C ont ete isoles au cours d'une epidemie de meningite a meningocoques qui a sevi entre janvier et mai 1979 dans l'est de la Haute-Volta, une region frappee jusqu'ici par une endemie et des epidemies de meningites a meningocoques du groupe A. Un total de 539 cas de meningite dont 55 mortels ont e signales, ce qui correspond a un taux d'atteinte de 517 cas pour 100 000. Ce taux etait plus eleve chez les enfants de moins de 15 ans. Les donnees cliniques et bacteriologiques laissent penser que les meningocoques du groupe C etaient resistants aux sulfa- mides. 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