Clone III-1 Research Articles

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

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

Epidemic spread of subgroup III of Neisseria meningitidis serogroup A to South Africa in 1996.

A total of 111 strains of Neisseria meningitidis isolated during a meningitis outbreak in Johannesburg, South Africa, in 1996 were analyzed by serogrouping, arbitrarily primed polymerase chain reaction analysis, ribotyping, and multilocus enzyme electrophoresis. Nineteen different clusters were identified, and typing patterns for the three techniques were comparable. Of the 111 strains analyzed, 55 (49.5%) belonged to the serogroup A clone complex designated internationally as subgroup I-1. The second largest cluster included 15 isolates (13.5%) that were identified as belonging to the pandemic clone III-1. A number of unrelated strains were also encountered. Our study provides the first documented evidence of the presence of clone III-1 in South Africa and indicates the continued spread of this clone well outside the African meningitis belt.

Les méningocoques à travers le monde : marqueurs phénotypiques et moléculaires

The first markers of meningococci were serogroup, defined by different polyosidic capsular immunospecifities (12 are described at present), and are still of great importance. Several other antigenic structures such as outer membrane proteins (OMPs) are used as markers : OMP serotypes of classes 2 and 3, OMP subtype of class 1. Serogroups, serotypes, subtypes and sometimes immunotypes (based on LPS) are associated in an antigenic formula (AF). At a world-wide level, the Electrophoretic Type (ET) defined by Multilocus Enzyme Electrophoresis (MLEE) is the most useful marker. For instance, the ET-5 and ET-37 have been described. The ET-5 was constituted primarily, but not exclusively, by strains of AF:B:15:P1.7,16 and B:4:P1.15. The ET-37 was constituted mostly by strains C:2a:P1.2,5. Two pandemics were due to Neisseria meningitidis serogroup A. They were mainly defined by MLEE. The first began in China in 1966, crossed Europe, and ended in Brazil in 1974 where it was responsible for a particularly widespread outbreak. The second pandemic, due to the same epidemic invasive strain A:4:P1.9/clone III-1 also began in China in 1983, spreading through Nepal, northern India. It was responsible for a severe oubreak in Mecca in August of 1987. It spread all around the world when the pilgrims returned to their countries. In countries with adequate health care facilities, the pandemic was stropped within two or three weeks. Unfortunately, in countries without these health care facilities, the spreading continues. For instance in Africa, specifically Niger, strains of this type continued to be isolated through the beginning of 1996. Molecular epidemiology markers like pulsotype and ribotype for instance, are able to demonstrate genetic variability between strains.

Characteristics of serogroup A Neisseria meningitidis strains isolated in the Central African Republic in February 1992.

A severe epidemic of serogroup A meningococcus meningitis occurred in the northwest Central African Republic from January to March 1992. Strains from 24 patients were characterized using serotyping, testing of susceptibility to antibiotics, and multilocus enzyme electrophoresis. In 23 of the 24 patients the causal strain was found to be 4:P1.9/clone III-1. These results indicate that such strains continue to spread in Africa and have taken hold in areas outside the "meningitis belt." This may be a consequence of changing climatic conditions.

Characterization ofNeisseria meningitidis serogroup A strains from an outbreak in France by serotype, serosubtype, multilocus enzyme genotype and outer membrane protein pattern

In an attempt to determine the epidemiological relationship between cases of infection caused by Neisseria meningitidis serogroup A in France between August 1987 and December 1988, and an outbreak which occurred in Mecca in August 1987, markers such as serotype, serosubtype, multilocus enzyme genotype and outer membrane protein (OMP) pattern were used to characterize the bacterial isolates. From a total of 28 cases, 20 strains were isolated. Sixteen isolates, including one which undoubtedly originated from the Mecca epidemic, were homogenous (serotype 4, serosubtype P1.9, multilocus enzyme genotype of clone III-1, identical OMP pattern). Four isolates had a different OMP pattern with little or no P1 protein, no P4 and no P6. Two of these isolates belonged to other clones (I.1 and group I) and they were considered to be unrelated to the Mecca epidemic strains. The origin of the remaining two isolates was not clear. It is concluded that the majority of the Neisseria meningitidis serogroup A strains recently isolated in France originate from the Mecca epidemic.

Characterization of epidemic and nonepidemic Neisseria meningitidis serogroup A strains from Sudan and Sweden

A random selection of 25 strains isolated during an epidemic caused by serogroup A Neisseria meningitidis in Sudan (1988), 3 preepidemic meningococcal strains (1985), and 26 serogroup A strains isolated from sporadic cases of meningitis in Sweden (1973 to 1987) were assessed for multilocus enzyme genotypes (ETs), DNA restriction enzyme patterns, outer membrane proteins, lipopolysaccharides, pilus formation, and antibiograms. All of the 25 Sudanese epidemic isolates and 22 of the Swedish strains were of the same or closely related ETs (ETs 3, 4, and 5), corresponding to clone III-1, which has been responsible for two pandemic waves in the last three decades. The earlier pandemic involved Scandinavia, and the last one caused an outbreak during the pilgrimage to Mecca, Saudi Arabia (August 1987), spreading to Sudan, Chad, and Ethiopia. The three Sudanese preepidemic isolates (1985) were clone IV-1 (sulfonamide susceptible), which has been resident in the African meningitis belt for the last 25 years. The uniformity of clone III-1 strains (all sulfonamide resistant) from Sudan and Sweden was confirmed by DNA restriction enzyme patterns. ETs 3, 4, and 5 from Sudan and Sweden had 86 to 100% similarity to a Swedish clone III-1 reference strain, whereas ETs 1, 2, 6, and 7 showed 50 to 80% similarity. Class 1 protein for clone III-1 showed serosubtype antigens P1.9 and P1.x, whereas ET6 strains (clone IV-1) had serosubtype P1.7. Lipopolysaccharides were variable in the Sudanese and Swedish strains. Pili were expressed in all clone III-1 isolates from Sudan and Sweden but in none of the clone IV-1 isolates (Sudan, 1985).

Serogroup A Neisseria meningitidis of Clone III-1 Present in Western Norway as Early as 1969–73

A clone of serogroup A Neisseria meningitidis recognized by multilocus enzyme electrophoresis and designated as clone III-1, has caused major epidemics of meningococcal disease in various parts of the world since the 1970s. In Norway, serogroup B meningococci have been responsible for an epidemic since the mid-1970s. We have studied a sample of 53 meningococci isolated from patients in western Norway prior to the serogroup B epidemic. 22/35 meningococcal isolates collected 1969-73 represented clone III-1, whereas this clone was not found in the 18 isolates from 1962-68. It has been speculated that the epidemic of meningococcal disease in Finland caused by clone III-1 in 1973-75 had spread from an epidemic in USSR that began in 1969. Our findings demonstrate, however, that the clone III-1 was present in Scandinavia in 1969.

Multilocus Enzyme Electrophoresis – Application to the Study of Meningococcal Meningitis and Listeriosis

Multilocus Enzyme Electrophoresis – Application to the Study of Meningococcal Meningitis and Listeriosis

Features of a Large Epidemic of Group A Meningococcal Meningitis in Khartoum, Sudan in 1988

A large epidemic (February-August 1988) of group A sulphonamide resistant, clone III-1 meningococcal meningitis in Khartoum, Sudan is described. A total of 10,099 cases were admitted to treatment centers with 8,397 cases during March and April, corresponding to an annual incidence of 1,679/100,000 inhabitants during this period. The age profile showed a high morbidity in adults (31% of the cases greater than or equal to 20 years). The male dominance was marked especially in the adult cases with a proportion of 3.2:1. The epidemic started during the hot and dry season and declined when the clouds came, humidity rose, temperature fell and a mass vaccination campaign had been implemented together with other epidemic precautions. Vaccination with a combined group A/C polysaccharide vaccine had been given 4 weeks-1 year before hospitalization to 11% of the children, 80% of whom were greater than 18 months of age. The estimated case fatality rate was 6.3%. Since 47% of the cases came from periurban and rural areas, the actual mortality during the epidemic might have been higher when considering those who may have died before reaching any of the treatment centres. Fatal cases had a short history of acute illness and a septic condition. Septicaemia was rare and seen in only 3.7% of the cases, the rest had acute purulent meningitis. Hearing loss/impairment and hemiplegia was diagnosed in 2-3% of the cases. The epidemiology, based on detailed typing/subtyping and restriction enzyme patterns of meningococcal strains, was apparently associated with the Mecca outbreak in August 1987.

Characteristics of Serogroup A Neisseria meningitidis Responsible for an Epidemic in Ethiopia, 1988-89

In September 1988, an epidemic of meningococcal disease started in Ethiopia. 21 Neisseria meningitidis isolates recovered from patients in Addis Ababa and towns 200 km south of the capital were characterized by serogrouping, serotyping, testing of susceptibility to antibiotics, restriction endonuclease fingerprinting, and multilocus enzyme electrophoresis. The 21 isolates were essentially homogeneous for all properties tested and belonged to clone III-1 of serogroup A N. meningitidis, which was also responsible for the epidemics in Saudi Arabia in 1987 and in Sudan and Chad in 1988.

Childhood Acute Bacterial Meningitis in the Suda: An Epidemiological, Clinical and Laboratory Study

The aims of the present study were to document the epidemiology, clinical features and complications of childhood acute bacterial meningitis (ABM) in The Sudan during both an inter-epidemic (endemic) period (1985-1986), and the 1988 serogroup A epidemic; and to examine the phenotypic and genetic similarities and differences of Neisseria meningitidis strains isolated in The Sudan and Sweden. A new enzyme immunoassay test (Pharmacia Meningitis EIA-Test) was evaluated as a potential rapid diagnostic method for the detection of Haemophilus influenzae (HI) type b, Neisseria meningitidis (MC) and Streptococcus pneumoniae (PNC). The test was found to have good sensitivity (0.86) and specificity (0.95) in the inter-epidemic period; and to be adaptable to the field work in The Sudan during the 1988 MC epidemic. During inter-epidemic (endemic) situations in The Sudan, greater than 90% of childhood ABM was caused by one of the three organisms, HI type b, MC and PNC. HI accounted for 57% of the cases. The peak incidence (76%) of HI cases was in infants (less than 12 months) similar to the situation in other African countries. The overall case fatality ratio was 18.6%. Prospective follow-up of survivors for 3-4 years revealed that an additional 43% either died or had permanent neurological complications, the most prevalent and persistent of which was sensorineural hearing loss recorded in 22% of long term survivors. Post-meningitic children were found to have significantly lower intelligence quotients (92.3 +/- 13.9) than their sibling controls (100.7 +/- 10.2, P = 0.029). Features of the large serogroup A sulphonamide resistant MC epidemic (February-August 1988) in Khartoum are described. An estimated annual incidence of 1,679/100,000 was recorded at the peak of the epidemic. The highest attack rate was in young children less than 5 years, as in many other African countries; nevertheless, a high morbidity was observed in adults (31% of the cases greater than or equal to 20 years). The clinical features, mortality (6.3%) and short term sequelae in Sudanese children were generally within the framework described for MC disease elsewhere. Detailed analysis of MC isolates from Sudan and Sweden by characterizing their electrophoretic enzyme types, DNA restriction endonuclease pattern and outer membrane proteins, revealed that serogroup A MC clone III-1 was responsible of The Sudan epidemic in 1988 and has been the dominant serogroup A organism in Sweden since 1973. The Sudanese strains isolated prior to the epidemic (1985) were clone IV-1.(ABSTRACT TRUNCATED AT 250 WORDS)