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      Serogroup X in Meningococcal Disease, Western Kenya

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          Abstract

          To the Editor: Although >12 different serogroups of Neisseria meningitidis exist, most disease outbreaks across the African meningitis epidemic belt are caused by serogroup A and, less frequently, by serogroups C and W135 ( 1 ). N. meningitidis serogroup X was first described in the 1960s and has been found to cause a few cases of invasive disease across North America, Europe, and Africa ( 2 ). In Africa, small serogroup X outbreaks have been described in Ghana (9 cases over a 2-year period) and in Niger (134 cases between 1995 and 2000) ( 3 , 4 ). In 2006, however, 51% of 1,139 confirmed cases of meningococcal meningitis in Niger were found to be caused by serogroup X ( 5 ). Before the 2005-06 meningococcal epidemic season, no published reports had described serogroup X isolates in East Africa. We report the involvement of N. meningitidis serogroup X in an outbreak of meningococcal disease in Western Kenya. In January 2006, the Ministry of Health of Kenya and Médecins sans Frontières were notified of a suspected meningococcal disease outbreak in West Pokot District, bordering Uganda, in Western Kenya. On the basis of the initial outbreak investigation, the outbreak was assessed to have begun in late December 2005. Subsequent active surveillance, using the same clinical case definition of sudden fever onset with stiff neck, altered mental status, or both, showed 74 suspected cases through mid-March 2006, with a case-fatality rate of 20%. No cases were reported after March 2006. Over the course of the outbreak, cerebrospinal fluid samples were obtained from 18 patients. Due to low population density, poor access to seminomadic populations, and the limited nature of the outbreak (relatively small numbers dispersed over a wide geographic region), obtaining specimens from untreated patients in West Pokot proved difficult. Three of the 5 first samples were found to show gram-negative diplococci on staining, the next 2 were negative on Pastorex rapid latex agglutination test (Bio-Rad Laboratories, Hercules, CA, USA) (during the outbreak investigation), and a subsequent 13 were sent to the African Medical and Research Foundation (AMREF) laboratory in Nairobi, Kenya, for culture and susceptibility testing. From these 13 specimens, 2 yielded a pure growth of N. meningitidis serogroup X, while no growth was observed for the remaining 11 specimens. These 2 cultures were subsequently confirmed as serogroup X by the World Health Organization Collaborating Centre for Meningococci in Oslo, Norway. Multilocus sequence typing and sequencing of the porA and fetA genes as described (http://pubmlst.org/neisseria/), showed that the infecting strain belonged to a new sequence type, ST-5403, and that it was subtype P1.19,26 and FetA type F3-27. This sequence type is unrelated to other serogroup X isolates from Africa, including those from the latest serogroup X outbreak in Niger, but it resembles a sequence type isolated in the United States in the 1970s. In addition to the testing at AMREF and in the Oslo laboratory, the 13 samples were also analyzed by PCR at the US Naval Medical Research Unit No. 3 in Cairo, Egypt. Overall, 5 of these 13 specimens were positive for serogroup X (including the 2 samples found to be serogroup X at AMREF and confirmed by PCR in Oslo) and 1 each was positive for serogroups C, W135, and Y. At the same time as this outbreak in Western Kenya, a meningococcal meningitis outbreak was being monitored across the border in the Karamoja region of northeastern Uganda. Seminomadic populations move freely across the 2 countries, and we can assume that there was 1 meningitis outbreak that started in eastern Uganda and spread to Western Kenya. Although initial laboratory testing in Uganda suggested the presence of serogroup A, among 23 specimens subsequently sent to the Oslo laboratory, 11 were identified as serogroup X by PCR and 3 were serogroup W135 ( 6 ). Therefore, the outbreaks in both Kenya and Uganda involved multiple N. meningitidis serogroups. In West Pokot, Kenya, the Ministry of Health and Médecins sans Frontières conducted a vaccination campaign using the trivalent polysaccharide vaccine against serogroups A, C, and W135. Before 2006, previous disease outbreaks caused by serogroup X had not reached the magnitude of those caused by serogroups A, C, or W135; they tended to evolve independently of the occurrence of both serogroups A and C and to be self-limited ( 3 , 4 ). Although most of Kenya is not included in the African meningitis belt, large epidemics of meningococcal disease have been reported previously ( 7 ). In conclusion, we would like to highlight the presence of N. meningitidis serogroup X in East Africa, its potential involvement in disease outbreaks, and the difficulties it may cause for laboratory confirmation and, consequently, for making an appropriate epidemic response.

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          Most cited references5

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          Molecular epidemiology of neisseria meningitidis isolated in the African Meningitis Belt between 1988 and 2003 shows dominance of sequence type 5 (ST-5) and ST-11 complexes.

          At the two World Health Organization Collaborating Centers for Reference and Research on Meningococci in Marseilles, France, and Oslo, Norway, the multilocus sequence typing technique was used for the characterization of a total of 357 strains of meningococci isolated from meningitis cases in 13 African countries of the meningitis belt between 1988 and 2003. Among these strains, 278 of 357 (77.9%) belonged to the sequence type 5 (ST-5) complex; 23.2% were ST-5 and 53.5% were ST-7. ST-5 was probably introduced in Africa in 1987 and was responsible for most of the meningitis cases between 1988 and 2001. ST-7 emerged in the mid-1990s and has totally replaced ST-5 since 2002. These two STs characterized serogroup A strains and have been responsible for hundreds of thousands of cases. Fifty-two strains (14.3%) belonged to the ST-11 complex. The ST-11 complex was characterized by serogroup W135, which has been responsible for an increasing number of sporadic cases since 2000 and the first W135 epidemic ever seen in Africa (in Burkina Faso in 2002). Identification of W135 ST-11 strains in many countries is a great concern for the region. Apart from these two major clonal complexes, a few other clones, such as ST-2881, ST-181, and ST-751, were sporadically detected. Careful surveys for these clones need to be conducted, but at present they play only a minor role in the overall epidemiology of meningococcal meningitis.
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            Prospective study of a serogroup X Neisseria meningitidis outbreak in northern Ghana.

            After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.
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              Outbreaks of serogroup X meningococcal meningitis in Niger 1995-2000.

              In the African meningitis belt, the recurrent meningococcal meningitis epidemics are generally caused by serogroup A. In the past 20 years, other serogroups have been detected, such as X or W135, which have caused sporadic cases or clusters. We report here 134 meningitis cases caused by Neisseria meningitidis serogroup X that occurred in Niamey between 1995 and 2000. They represented 3.91% of the meningococcal isolates from all CSF samples, whereas 94.4% were of serogroup A. Meningococcal meningitis cases were detected using the framework of the routine surveillance system for reportable diseases organized by the Ministry of Public Health of Niger. The strains were isolated and determined by the reference laboratory for meningitis in Niamey (CERMES) and further typed at the WHO collaborating center of the Pharo in Marseille and at the National Reference Center for the Meningococci at the Institut Pasteur. Reference laboratories in Marseille and Paris characterized 47 isolates having the antigenic formula (serogroup:serotype:sero-subtype) X:NT:P1.5. Meningitis cases due to meningococcus serogroup X did not present any clinical or epidemiological differences to those due to serogroup A. The seasonal incidence was classical; 93.3% of the cases were recorded during the dry season. The mean age of patients was 9.2 years (+/- 6 years). The sex ratio M/F was 1.3. Case fatality rate was 11.9% without any difference related to age or sex. The increasing incidence of the serogroup X was not related to the decrease of serogroup A, but seemed cyclic, and evolved independently of the recurrence of both serogroups A and C.
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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                June 2007
                : 13
                : 6
                : 944-945
                Affiliations
                [* ]African Medical and Research Foundation, Nairobi, Kenya
                []Médecins Sans Frontières–Spain, Nairobi, Kenya
                [3]Ministry of Health, Nairobi, Kenya
                [§ ]Norwegian Institute of Public Health, Oslo, Norway
                Author notes
                Address for correspondence: Helen S. Cox, Burnet Institute for Medical Research and Public Health, PO Box 2284, Melbourne, Victoria 3001, Australia; email: hcox@ 123456burnet.edu.au
                Article
                07-0042
                10.3201/eid1306.070042
                2792864
                17582900
                f6728bf3-e1de-408c-b81f-eb483b9dcfb8
                History
                Categories
                Letters to the Editor

                Infectious disease & Microbiology
                meningitis,outbreak,letter,serogroup x
                Infectious disease & Microbiology
                meningitis, outbreak, letter, serogroup x

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